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Cell culture models of oral mucosal barriers: A review with a focus on applications, culture conditions and barrier properties

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Article: 1479568 | Received 15 May 2018, Accepted 17 May 2018, Published online: 25 Sep 2018

References

  • Ganz T. Epithelia: not just physical barriers. Proc Natl Acad Sci U S A. 2002;99(6):3357–8. doi:10.1073/pnas.072073199.
  • Richter JF, et al. A novel method for imaging sites of paracellular passage of macromolecules in epithelial sheets. J Control Release. 2016;229:70–9. doi:10.1016/j.jconrel.2016.03.018.
  • Presland RB, Jurevic RJ. Making sense of the epithelial barrier: what molecular biology and genetics tell us about the functions of oral mucosal and epidermal tissues. J Dent Educ. 2002;66(4):564–74.
  • Li Q, et al. Interferon-gamma and tumor necrosis factor-alpha disrupt epithelial barrier function by altering lipid composition in membrane microdomains of tight junction. Clin Immunol. 2008;126(1):67–80. doi:10.1016/j.clim.2007.08.017.
  • Ye D, Ma I, Ma TY. Molecular mechanism of tumor necrosis factor-alpha modulation of intestinal epithelial tight junction barrier. Am J Physiol Gastrointest Liver Physiol. 2006;290(3):G496–504. doi:10.1152/ajpgi.00318.2005.
  • Ma TY, et al. TNF-alpha-induced increase in intestinal epithelial tight junction permeability requires NF-kappa B activation. Am J Physiol Gastrointest Liver Physiol. 2004;286(3):G367–76. doi:10.1152/ajpgi.00173.2003.
  • Abe A, et al. Interferon-gamma increased epithelial barrier function via upregulating claudin-7 expression in human submandibular gland duct epithelium. J Mol Histol. 2016;47(3):353–63. doi:10.1007/s10735-016-9667-2.
  • Mei M, et al. Claudin-3 is required for modulation of paracellular permeability by TNF-α through ERK1/2/slug signaling axis in submandibular gland. Cell Signal. 2015;27:10. doi:10.1016/j.cellsig.2015.07.002.
  • Baker OJ, et al. Proinflammatory cytokines tumor necrosis factor-alpha and interferon-gamma alter tight junction structure and function in the rat parotid gland Par-C10 cell line. Am J Physiol Cell Physiol. 2008;295(5):C1191–201. doi:10.1152/ajpcell.00144.2008.
  • Banks WA. From blood-brain barrier to blood-brain interface: new opportunities for CNS drug delivery. Nat Rev Drug Discov. 2016;15(4):275–92. doi:10.1038/nrd.2015.21.
  • Wigley C. Chapter 33, Oral Cavity. [book auth.] Standring S Berkovitz BKB. Gray’s Anatomy. 2005:581–606. 39.
  • Salamat-Miller N, Chittchang M, Johnston TP. The use of mucoadhesive polymers in buccal drug delivery. Adv Drug Deliv Rev. 2005;57(11):1666–91. doi:10.1016/j.addr.2005.07.003.
  • Reddy PC, Chaitanya KSC, Madhusudan Rao Y. A review on bioadhesive buccal drug delivery systems: current status of formulation and evaluation methods. Daru. 2011;19(6):385–403.
  • Kulkarni UD, et al. Effect of Experimental Temperature on the Permeation of Model Diffusants Across Porcine Buccal Mucosa. AAPS PharmSciTech. 2011;12(2):579–86. doi:10.1208/s12249-011-9624-z.
  • Consortium, International Transporter, et al. Membrane transporters in drug development. Nat Rev Drug Discov. 2010;9(3):215–36. doi:10.1038/nrd3028.
  • Li Y, Lu J, Paxton JW. The role of ABC and SLC transporters in the pharmacokinetics of dietary and herbal phytochemicals and their interactions with xenobiotics. Curr Drug Metab. 2012;13(5):624–39. doi:10.2174/1389200211209050624.
  • Lin L, et al. SLC transporters as therapeutic targets: emerging opportunities. Nat Rev Drug Discov. 2015;14(8):543–60. doi:10.1038/nrd4626.
  • Morrissey KM, et al. The UCSF-FDA TransPortal: a public drug transporter database. Clin Pharmacol Ther. 2012;92(5):545–6. doi:10.1038/clpt.2012.44.
  • Nishimura M, Naito S. Tissue-specific mRNA expression profiles of human ATP-binding cassette and solute carrier transporter superfamilies. Drug Metab Pharmacokinet. 2005;20(6):452–77. doi:10.2133/dmpk.20.452.
  • DeGorter MK, et al. Drug transporters in drug efficacy and toxicity. Annu Rev Pharmacol Toxicol. 2012(52):249–73. doi:10.1146/annurev-pharmtox-010611-134529.
  • Nigam SK. What do drug transporters really do? Nat Rev Drug Discov. 2015;14(1):29–44. doi:10.1038/nrd4461.
  • Nałęcz KA. Solute Carriers in the Blood-Brain Barier: Safety in Abundance. Neurochem Res. 2016; 42(3):795–809. doi:10.1007/s11064-016-2030-x.
  • Mahringer A, Fricker G. ABC transporters at the blood-brain barrier. Expert Opin Drug Metab Toxicol. 12(5):499–508. doi:10.1517/17425255.2016.1168804.
  • Seeger MA, van Veen HW. Molecular basis of multidrug transport by ABC transporters. Biochim Biophys Acta. 2009;1794(5):725–37. doi:10.1016/j.bbapap.2008.12.004.
  • Tarling EJ, de Aguiar Vallim TQ, Edwards PA. Role of ABC transporters in lipid transport and human disease. Trends Endocrinol Metab. 2013;24(7):342–50. doi:10.1016/j.tem.2013.01.006.
  • Kaminski WE, Piehler A, Wenzel JJ. ABC A-subfamily transporters: structure, function and disease. Biochim Biophys Acta. 2006;1762(5):510–24. doi:10.1016/j.bbadis.2006.01.011.
  • Hediger MA, et al. The ABCs of membrane transporters in health and disease (SLC series): introduction. Mol Aspects Med. 2013; 34 (2–3): 95–107. doi:10.1016/j.mam.2012.12.009.
  • Kulkarni PS, et al. Characterization of human buccal epithelial cells transfected with the simian virus 40 T-antigen gene. Carcinogenesis. 1995;16(10):2515–21. doi:10.1093/carcin/16.10.2515.
  • Tsukita S, Furuse M, Itoh M. Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol. 2001;2(4):285–93. doi:10.1038/35067088.
  • Zihni C, et al. Tight junctions: from simple barriers to multifunctional molecular gates. Nat Rev Mol Cell Biol. 2016;17(9):564–80. doi:10.1038/nrm.2016.80.
  • Mineta K, Yamamoto Y, Yamazaki Y, Tanaka H, Tada Y, Saito K, Tamura A, Igarashi M, Endo T, Takeuchi K, Tsukita S. Predicted expansion of the claudin multigene family. FEBS Lett. 2011; 18;585( 4):606–12. doi:10.1016/j.febslet.2011.01.028.
  • Günzel D, Fromm M. Claudins and other tight junction proteins. Compr Physiol. 2012;2( 3): 1819–52. 2012.
  • Canfield SG, Stebbins MJ, Morales BS, Asai SW, Vatine GD, Svendsen CN, Palecek SP, Shusta EV. An isogenic blood-brain barrier model comprising brain endothelial cells, astrocytes, and neurons derived from human induced pluripotent stem cells. J Neurochem. 2017;140(6):874–88. doi:10.1111/jnc.13923.
  • Appelt-Menzel A, Cubukova A, Günther K, Edenhofer F, Piontek J, Krause G, Stüber T, Walles H, Neuhaus W, Metzger M. Establishment of a Human Blood-Brain Barrier Co-culture Model Mimicking the Neurovascular Unit Using Induced Pluri- and Multipotent Stem Cells. Stem Cell Reports. 2017;8(4):894–906. doi:10.1016/j.stemcr.2017.02.021.
  • Matoltsy AG, Parakkal PF. Membrane-coating granules of keratinizing epithelia. J Cell Biol. 1965;24:297–307. doi:10.1083/jcb.24.2.297.
  • Hayward AF. Membrane-coating granules. Int Rev Cytol. 1979;95:97–127. doi:10.1016/S0074-7696(08)61661-7.
  • Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. s.l.: New York: Garland Science; 2002.
  • Yasen A, Herrera R, Rosbe K, Lien K, Tugizov SM. HIV internalization into oral and genital epithelial cells by endocytosis and macropinocytosis leads to viral sequestration in the vesicles. Virology. 2018;515:92–107. doi:10.1016/j.virol.2017.12.012.
  • Drago L, Mombelli B, De Vecchi E, Bonaccorso C, Fassina MC, Gismodo MR. Candida albicans cellular internalization: a new pathogenic factor? Int J Antimicrob Agents. 2000;6(4):545–7. doi:10.1016/S0924-8579(00)00296-X.
  • Solis NV, Swidergall M, Bruno VM, Gaffen SL, Filler SG. The Aryl-Hydrocarbon Receptor governs epithelial cell invasion during oropharyngeal candidiasis. MBio. 2017;8(2), pii: e00025–17. doi:10.1128/mBio.00025-17.
  • Michalczyk A, Varigos G, Smith L, Ackland ML. Fresh and cultured buccal cells as a source of mRNA and protein for molecular analysis. Biotechniques. 2004;37(2):262–4,266-9. 37(2);262-4, 266-9, 2004. doi:10.2144/04372RR03.
  • Takeuchi H, Furuta N, Morisaki I, Amano A. Exit of intracellular Porphyromonas gingivalis from gingival epithelial cells is mediated by endocytic recycling pathway. Cell Microbiol. 2011;13(5):677–91. doi:10.1111/j.1462-5822.2010.01564.x.
  • Du W, Fan Y, Zheng N, He B, Yuan L, Zhang H, Wang X, Wang J, Zang X, Zhang Q. Transferrin receptor specific nanocarriers conjugated with functional 7peptide for oral delivery. Biomaterials. 2013;34(3):794–806. doi:10.1016/j.biomaterials.2012.10.003.
  • Ivanov AI, Nusrat A, Parkos CA. Endocytosis of the apical junctional complex: mechanisms and possible roles in regulation of epithelial barriers. Bioessays. 2005;27(4):356–65. doi:10.1002/bies.20203.
  • Utech M, et al. Mechanism of IFN-gamma-induced endocytosis of tight junction proteins: myosin II-dependent vacuolarization of the apical plasma membrane. Mol Biol Cell. 2005;16(10):5040–52. doi:10.1091/mbc.e05-03-0193.
  • Harhaj NS, Barber AJ, Antonetti DA. Platelet-derived growth factor mediates tight junction redistribution and increases permeability in MDCK cells. J Cell Physiol. 2002;193(3):349–64. doi:10.1002/jcp.10183.
  • Hopkins AM, et al. Constitutive activation of Rho proteins by CNF-1 influences tight junction structure and epithelial barrier function. J Cell Sci. 2003;116(Pt 4):725–42. doi:10.1242/jcs.00300.
  • Kowalczyk AP, Nanes BA. Adherens junction turnover: regulating adhesion through cadherin endocytosis, degradation, and recycling. Subcell Biochem. 2012(60):197–222. doi:10.1007/978-94-007-4186-7_9.
  • Linden SK, et al. Mucins in the mucosal barrier to infection. Mucosal Immunol. 2008;1(3):183–97. doi:10.1038/mi.2008.5.
  • Alemka A, Corcionivoschi N, Bourke B. Defense and adaptation: the complex inter-relationship between Campylobacter jejuni and mucus. Front Cell Infect Microbiol. 2012;2:15. doi:10.3389/fcimb.2012.00015.
  • Corfield AP. Mucins: a biologically relevant glycan barrier in mucosal protection. Biochim Biophys Acta. 2015;1850(1):236–52. doi:10.1016/j.bbagen.2014.05.003.
  • Dodds M, et al. Saliva A review of its role in maintaining oral health and preventing dental disease. BDJ Team. 2015; 2. doi:10.1038/bdjteam.2015.123.
  • Marcotte H, Lavoie MC. Oral microbial ecology and the role of salivary immunoglobulin A. Microbiol Mol Biol Rev. 1998;62(1):71–109.
  • McGuckin MA, et al. Mucin dynamics and enteric pathogens. Nat Rev Microbiol. 2011;9(4):265–78. doi:10.1038/nrmicro2538.
  • Benson K, Cramer S, Galla HJ. Impedance-based cell monitoring: barrier properties and beyond. Fluids Barriers CNS. 2013;10(1):5. doi:10.1186/2045-8118-10-5.
  • Tanaka H, Yamamoto Y, Kashihara H, Yamazaki Y, Tani K, Fujiyoshi Y, Mineta K, Takeuchi K, Tamura A, Tsukita S. Claudin-21 Has a Paracellular Channel Role at Tight Junctions. Molecular and Cellular Biology. 2016;6:954–64. doi:10.1128/MCB.00758-15.
  • Günzel D, Yu ASL. Claudins and the modulation of tight junction permeability. Physiol Rev. 2013;93:525–69. doi:10.1152/physrev.00019.2012.
  • Srinivasan B, et al. TEER measurement techniques for in vitro barrier model systems. J Lab Autom. 2015;20(2):107–26. doi:10.1177/2211068214561025.
  • Neuhaus W, Bogner E, Wirth M, Trzeciak J, Lachmann B, Gabor F, Noe CR. A novel tool to characterize paracellular transport: the APTS-dextran ladder. Pharm Res. 2006;23(7):1491–501. doi:10.1007/s11095-006-0256-z.
  • Sun H, Pang KS. Permeability, transport, and metabolism of solutes in Caco-2 cell monolayers: a theoretical study. Drug Metab Dispos. 2008;36(1):102–23. doi:10.1124/dmd.107.015321.
  • Neuhaus W. Development and validation of in-vitro models of the blood-brain barrier. Dissertation. Vienna: s.n., 2007.
  • Rupniak HT, et al. Characteristics of four new human cell lines derived from squamous cell carcinomas of the head and neck. J Natl Cancer Inst. 1985;75(4):621–35.
  • Jacobsen J, et al. TR146 cells grown on filters as a model for human buccal epithelium: I. Morphology, growth, barrier properties, and permeability. Int J Pharm. 1995;125:165–84. doi:10.1016/0378-5173(95)00109-V.
  • Jacobsen J, et al. Filter-grown TR146 cells as an in vitro model of human buccal epithelial permeability. Eur J Oral Sci. 1999;107(2):138–46. doi:10.1046/j.0909-8836.1999.eos107210.x.
  • Nielsen HM, et al. TR146 cells grown on filters as a model of human buccal epithelium: permeability of fluorescein isothiocyanate-labelled dextrans in the presence of sodium glycocholate. J Control Release. 1999;60;(2-3):223–33. doi:10.1016/S0168-3659(99)00081-4.
  • Nielsen HM, Rassing MR. TR146 cells grown on filters as a model of human buccal epithelium: V. Enzyme activity of the TR146 cell culture model, human buccal epithelium and porcine buccal epithelium, and permeability of leu-enkephalin. Int J Pharm. 2000;200(2):261–70. doi:10.1016/S0378-5173(00)00394-X.
  • Nielsen HM, Rassing MR. Nicotine permeability across the buccal TR146 cell culture model and porcine buccal mucosa in vitro: Effect of pH and concentration. Eur J Pharm Sci. 2002;16(3):151–7. doi:10.1016/S0928-0987(02)00083-0.
  • Nielsen HM, Rassing MR. TR146 cells grown on filters as a model of human buccal epithelium: IV. Permeability of water, mannitol, testosterone and beta-adrenoceptor antagonists. Comparison to human, monkey and porcine buccal mucosa. Int J Pharm. 2000;194(2):155–67. doi:10.1016/S0378-5173(99)00368-3.
  • Gumbleton M, Audus KL. Progress and limitations in the use of in vitro cell cultures to serve as a permeability screen for the blood-brain barrier. J Pharm Sci. 2001;90(11):1681–98. doi:10.1002/jps.1119.
  • Deli MA, et al. Permeability studies on in vitro blood-brain barrier models: physiology, pathology, and pharmacology. Cell Mol Neurobiol. 2005;25(1):59–127. doi:10.1007/s10571-004-1377-8.
  • Zhang H, Zhang J, Streisand JB. Oral mucosal drug delivery: clinical pharmacokinetics and therapeutic applications. Clin Pharmacokinet. 2002;41(9):661–80. doi:10.2165/00003088-200241090-00003.
  • Sander C, Nielsen HM, Jacobsen J. Buccal delivery of metformin: TR146 cell culture model evaluating the use of bioadhesive chitosan discs for drug permeability enhancement. Int J Pharm. 2013;458(2):254–61. doi:10.1016/j.ijpharm.2013.10.026.
  • Portero A, Remuñán-López C, Nielsen HM. The potential of chitosan in enhancing peptide and protein absorption across the TR146 cell culture model-an in vitro model of the buccal epithelium. Pharm Res. 2002;19(2):169–74. doi:10.1023/A:1014220832384.
  • Klemetsrud T, et al. Polymer coated liposomes for use in the oral cavity - A study of the in vitro toxicity, effect on cell permeability and interaction with mucin. J Liposome Res. 2016;3:1–37.
  • Iyire A, Alayedi M and Mohammed AR. Pre-formulation and systematic evaluation of amino acid assisted permeability of insulin across in vitro buccal cell layers. Sci Rep. 2016;6:32498. doi:10.1038/srep32498.
  • Pistone S, et al. Formulation of polysaccharide-based nanoparticles for local administration into the oral cavity. Eur J Pharm Sci. 2016;96:381–9. doi:10.1016/j.ejps.2016.10.012.
  • Kaiser M, et al. In Vitro and Sensory Evaluation of Capsaicin-Loaded Nanoformulations. PLoS One. 2015;10:10. doi:10.1371/journal.pone.0141017.
  • Zeng N, et al. Poloxamer bioadhesive hydrogel for buccal drug delivery: Cytotoxicity and trans-epithelial permeability evaluations using TR146 human buccal epithelial cell line. Int J Pharm. 2015;495(2):1028–37. doi:10.1016/j.ijpharm.2015.09.045.
  • Caon T, et al. Enhancing the buccal mucosal delivery of peptide and protein therapeutics. Pharm Res. 2015;32(1):1–21. doi:10.1007/s11095-014-1485-1.
  • Park K, Morishita M. Biodrug Delivery Systems: fundamentals, applications and clinical development. [Online] [Cited: November 28, 2016]. https://books.google.at/books?id=91jvBQAAQBAJ&pg=PA122&lpg=PA122&dq=buccal+mucosa+barrier&source=bl&ots=pLjmJZyF2e&sig=gtj0OL0HtmyjGTzSADGWn6Q0LIw&hl=de&sa=X&ved=0ahUKEwj4pdTu78DQAhUFLsAKHfvlAAIQ6AEIVTAL#v=onepage&q=buccal%20mucosa%20barrier&f=false.
  • Sohi H, et al. Critical evaluation of permeation enhancers for oral mucosal drug delivery. Drug Dev Ind Pharm. 2010;36(3):254–82. doi:10.3109/03639040903117348.
  • Lermann U, Morschhäuser J. Secreted aspartic proteases are not required for invasion of reconstituted human epithelia by Candida albicans. Microbiology. 2008;154(Pt 11):3281–3295. doi:10.1099/mic.0.2008/022525-0.
  • Moyes DL, et al. A biphasic innate immune MAPK response discriminates between the yeast and hyphal forms of Candida albicans in epithelial cells. Cell Host Microbe. 2010;8(3):225–35. doi:10.1016/j.chom.2010.08.002.
  • Samaranayake YH, et al. Differential phospholipase gene expression by Candida albicans in artificial media and cultured human oral epithelium. APMIS. 2006;114(12):857–66. doi:10.1111/j.1600-0463.2006.apm_479.x.
  • Senel S, et al. Enhancing effect of chitosan on peptide drug delivery across buccal mucosa. 2000;21(20):2067–71.
  • Wertz PW, Squier CA. Cellular and molecular basis of barrier function in oral epithelium. Crit Rev Ther Drug Carrier Syst. 1991;8(3):237–69.
  • Teubl BJ, et al. The oral cavity as a biological barrier system: design of an advanced buccal in vitro permeability model. Eur J Pharm Biopharm. 2013;84(2):386–93. doi:10.1016/j.ejpb.2012.10.021.
  • Cone RA. Barrier properties of mucus. Adv Drug Deliv Rev. 2009;61(2):75–85. doi:10.1016/j.addr.2008.09.008.
  • Yadev NP, et al. Evaluation of tissue engineered models of the oral mucosa to investigate oral candidiasis. Microb Pathog. 2011;50(6):278–85. doi:10.1016/j.micpath.2010.11.009.
  • Miyauchi S, et al. Establishment of human tumor cell line (Ueda-1) derived from squamous cell carcinoma of the floor of the mouth. Jpn J Oral. Maxillofac. Surg. 1985;31:1347–51. in Japanese, not available. doi:10.5794/jjoms.31.1347.
  • Wang Y, et al. Evaluation of HO-1-u-1 cell line as an in vitro model for sublingual drug delivery involving passive diffusion–Initial validation studies. Int J Pharm. 2007; 334 (1–2): 27–34. doi:10.1016/j.ijpharm.2006.10.012.
  • Narang N, Sharma J. Sublingual Mucosa as a route for systemic drug delivery. Int J Pharm Pharmaceutical Sci. 2011;3(2):18–22.
  • Wang Y, Zuo Z, Chow MS. HO-1-u-1 model for screening sublingual drug delivery–influence of pH, osmolarity and permeation enhancer. Int J Pharm. 2009; 370 (1–2): 68–74. doi:10.1016/j.ijpharm.2008.11.010.
  • Hiroshima Y, et al. Effect of Hangeshashinto on calprotectin expression in human oral epithelial cells. Odontology. 2016;104(2):152–62. doi:10.1007/s10266-015-0196-3.
  • O’Callaghan K, et al. Induction of apoptosis in oral squamous carcinoma cells by pyrrolo-1,5-benzoxazepines. Mol Med Rep. 2015;12(3):3748–54. doi:10.3892/mmr.2015.3832.
  • Khammanivong A, et al. S100A8/A9 (calprotectin) negatively regulates G2/M cell cycle progression and growth of squamous cell carcinoma. PLoS One. 2013;8:7. doi:10.1371/journal.pone.0069395.
  • Lermann U, Morschhäuser J. Secreted aspartic proteases are not required for invasion of reconstituted human epithelia by Candida albicans. Microbiology. 2008;154(Pt 11):3281–95. doi:10.1099/mic.0.2008/022525-0.
  • Reiss M, Pitman SW, Sartorelli AC. Modulation of the terminal differentiation of human squamous carcinoma cells in vitro by all-trans-retinoic acid. J Natl Cancer Inst. 1985;74(5):1015–23.
  • Hansson A, et al. Expression of keratins in normal, immortalized and malignant oral epithelia in organotypic culture. Oral Oncol. 2001;37(5):419–30. doi:10.1016/S1368-8375(00)00089-0.
  • Ceder R, et al. The application of normal, SV40 T-antigen-immortalised and tumour-derived oral keratinocytes, under serum-free conditions, to the study of the probability of cancer progression as a result of environmental exposure to chemicals. Altern Lab Anim. 2007;35(6):621–39.
  • Whang YM, et al. Hyperacetylation enhances the growth-inhibitory effect of all-trans retinoic acid by the restoration of retinoic acid receptor beta expression in head and neck squamous carcinoma (HNSCC) cells. Cancer Chemother Pharmacol. 2005;56(5):543–55. doi:10.1007/s00280-004-0970-3.
  • Sarang Z, et al. Microarray assessment of fibronectin, collagen and integrin expression and the role of fibronectin-collagen coating in the growth of normal, SV40 T-antigen-immortalised and malignant human oral keratinocytes. Altern Lab Anim. 2003;31(6):575–85.
  • Chun SG, et al. Targeted inhibition of histone deacetylases and hedgehog signaling suppress tumor growth and homologous recombination in aerodigestive cancers. Am J Cancer Res. 2015;5(4):1337–52.
  • Moroyama T, et al. Establishment and characterization of a human tumor cell line (Nakata-1) derived from squamous carcinoma of the buccal mucosa. Proc Jpn Can Assoc. 1986;45: 242.not available.
  • Sato K, et al. RANKL synthesized by both stromal cells and cancer cells plays a crucial role in osteoclastic bone resorption induced by oral cancer. Am J Pathol. 2013;182(5):1890–9. doi:10.1016/j.ajpath.2013.01.038.
  • Ohshima M, et al. Physiologic levels of epidermal growth factor in saliva stimulate cell migration of an oral epithelial cell line, HO-1-N-1. Eur J Oral Sci. 2002;110(2):130–6. doi:10.1034/j.1600-0722.2002.11179.x.
  • Laheij AM, et al. The impact of virulence factors of Porphyromonas gingivalis on wound healing in vitro. J Oral Microbiol. 2015;7:27543. doi:10.3402/jom.v7.27543.
  • Hayashi K, et al. Effect of 9-cis-retinoic acid on oral squamous cell carcinoma cell lines. Cancer Lett. 2000;151(2):199–208. doi:10.1016/S0304-3835(99)00422-X.
  • Hayashi K, et al. Overexpression of retinoic acid receptor beta induces growth arrest and apoptosis in oral cancer cell lines. Jpn J Cancer Res. 2001;92(1):42–50. doi:10.1111/j.1349-7006.2001.tb01046.x.
  • Prime SS, et al. The behaviour of human oral squamous cell carcinoma in cell culture. J Pathol. 1990;160(3):259–69. doi:10.1002/path.1711600313.
  • Yee M, et al. Porphyromonas gingivalis stimulates IL-6 and IL-8 secretion in GMSM-K, HSC-3 and H413 oral epithelial cells. Anaerob. 2014;28:62–7. doi:10.1016/j.anaerobe.2014.05.011.
  • Guo W, et al. CD24 activates the NLRP3 inflammasome through c-Src kinase activity in a model of the lining epithelium of inflamed periodontal tissues. Immun Inflamm Dis. 2014;2(4):239–53. doi:10.1002/iid3.40.
  • Ye P. Modulation of epithelial tight junctions by TGF-beta 3 in cultured oral epithelial cells. Aust Dent J. 2012;57(1):11–7. doi:10.1111/j.1834-7819.2011.01651.x.
  • Narayanan SP, et al. Integrated genomic analyses identify KDM1A’s role in cell proliferation via modulating E2F signaling activity and associate with poor clinical outcome in oral cancer. Cancer Lett. 2015;367(2):162–72. doi:10.1016/j.canlet.2015.07.022.
  • Ye P, et al. Differential expression of transforming growth factors-beta 1, -beta 2, -beta 3 and the type I, II, III receptors in the lining epithelia of inflamed gingiva. Pathology. 2003;35(5):384–92. doi:10.1080/00313020310001602585.
  • Lee EJ, et al. Characterization of newly established oral cancer cell lines derived from six squamous cell carcinoma and two mucoepidermoid carcinoma cells. Exp Mol Med. 2005;37(5):379–90. doi:10.1038/emm.2005.48.
  • Kim YK, Koo NY, Yun PY. Anticancer effects of CKD-602 (Camtobell®) via G2/M phase arrest in oral squamous cell carcinoma cell lines. Oncol Lett. 2015;9(1):136–42. doi:10.3892/ol.2014.2648.
  • Cho JH, et al. The bacterial protein azurin enhances sensitivity of oral squamous carcinoma cells to anticancer drugs. Yonsei Med J. 2011;52(5):773–8. doi:10.3349/ymj.2011.52.5.773.
  • Park SR, et al. Pseudomonas aeruginosa exotoxin A reduces chemoresistance of oral squamous carcinoma cell via inhibition of heat shock proteins 70 (HSP70). Yonsei Med J. 2010;51:5. doi:10.3349/ymj.2010.51.5.708.
  • Moon, Y, et al. Effect of CD133 overexpression on the epithelial-to-mesenchymal transition in oral cancer cell lines. Clin Exp Metastasis. 2016;33(5):487–96. doi:10.1007/s10585-016-9793-y.
  • Lin, SC, et al. Establishment of OC3 oral carcinoma cell line and identification of NF-kappa B activation responses to areca nut extract. J Oral Pathol Med. 2004;33(2);79–86. doi:10.1111/j.1600-0714.2004.00034.x.
  • Chen, YH, et al. Apoptotic effect of cisplatin and cordycepin on OC3 human oral cancer cells. Chin J Integr Med. 2014;20(8):624–32. doi:10.1007/s11655-013-1453-3.
  • Wu, SY, Wu, AT, Liu, SH. Microrna-17-5p regulated apoptosis-related protein expression and radiosensitivity in oral squamous cell carcinoma caused by betel nut chewing. Oncotarget. 2016;7(32):51482–51493. doi:10.18632/oncotarget.9856.
  • Hsiao, JR, Leu, SF, Huang, BM. Apoptotic mechanism of paclitaxel-induced cell death in human head and neck tumor cell lines. J Oral Pathol Med. 2009;38(2):188–97. doi:10.1111/j.1600-0714.2008.00732.x.
  • Wang, SH, Chang, CW, Chou, HC. 5-Methoxytryptophan-dependent inhibition of oral squamous cell carcinoma metastasis. Electrophoresis. 2015;36(17), pp. 2027–34. doi:10.1002/elps.201500154.
  • Kok, SH, et al. Establishment and characterization of a tumorigenic cell line from areca quid and tobacco smoke-associated buccal carcinoma. Oral Oncol. 2007;43(7):639–47. doi:10.1016/j.oraloncology.2006.07.007.
  • Lin, CS, et al. Silencing JARID1B suppresses oncogenicity, stemness and increases radiation sensitivity in human oral carcinoma. 2015;368(1);36–45.
  • Lee, CH, et al. IL-1β promotes malignant transformation and tumor aggressiveness in oral cancer. J Cell Physiol. 2015;230(4):875–84. doi:10.1002/jcp.24816.
  • Chang, CC, et al. MicroRNA-17/20a functions to inhibit cell migration and can be used a prognostic marker in oral squamous cell carcinoma. Oral Oncol. 2013;49(9):923–31. doi:10.1016/j.oraloncology.2013.03.430.
  • Chang, CC, et al. HDAC2 promotes cell migration/invasion abilities through HIF-1α stabilization in human oral squamous cell carcinoma. J Oral Pathol Med. 2011;40(7):567–75. doi:10.1111/j.1600-0714.2011.01009.x.
  • Gioanni, J, et al. Two new human tumor cell lines derived from squamous cell carcinomas of the tongue: establishment, characterization and response to cytotoxic treatment. Eur J Cancer Clin Oncol. 1988;24(9);1445–55. doi:10.1016/0277-5379(88)90335-5.
  • Zhang, Z, et al. Hyaluronan synthase 2 expressed by cancer-associated fibroblasts promotes oral cancer invasion. 2016;35(1):181. doi:10.1186/s13046-016-0458-0.
  • Li, YC, et al. SATB1 promotes tumor metastasis and invasiveness in oral squamous cell carcinoma. Oral Dis. 2016; 23(2):247–254. doi:10.1111/odi.12602.
  • Zhang, X, et al. Knockdown of Myosin 6 inhibits proliferation of oral squamous cell carcinoma cells. J Oral Pathol Med. 2016;45(10):740–5. doi:10.1111/jop.12448.
  • Bozec, A, et al. Combination of phosphotidylinositol-3-kinase targeting with cetuximab and irradiation: A preclinical study on an orthotopic xenograft model of head and neck cancer. Head Neck. 2017;39(1):151–159.  doi:10.1002/hed.24560.
  • Tonissi, F, et al. Reoxygenation Reverses Hypoxia-related Radioresistance in Head and Neck Cancer Cell Lines. 2016;36(5):2211–5.
  • Stojanović, N, et al. Integrin αvβ3 expression in tongue squamous carcinoma cells Cal27 confers anticancer drug resistance through loss of pSrc(Y418). Biochim Biophys Acta. 2016;1863(8):1969–78. doi:10.1016/j.bbamcr.2016.04.019.
  • Mo, H, et al. Expression, roles and therapy target values of CD24 in oral squamous cell carcinoma. Beijing Da Xue Xue Bao. 2016;48(1):16–22. Article in Chinese.
  • Ma, Z, Bi, Q and Wang, Y. Hydrogen sulfide accelerates cell cycle progression in oral squamous cell carcinoma cell lines. Oral Dis. 2015;21(2):156–62. doi:10.1111/odi.12223.
  • Cui, Z, et al. TRIM24 overexpression is common in locally advanced head and neck squamous cell carcinoma and correlates with aggressive malignant phenotypes. PLoS One. 2013;8(5):e63887. doi:10.1371/journal.pone.0063887.
  • Wu, HH, et al. Bevacizumab regulates cancer cell migration by activation of STAT3. Asian Pac J Cancer Prev. 2015;16(5):6501–6. doi:10.7314/APJCP.2015.16.15.6501.
  • Cheung, J, et al. A nonviral vector with transfection activity comparable with adenoviral transduction. Ther Deliv. 2016;7(11):739–49. doi:10.4155/tde-2016-0054.
  • Sapkota, D, et al. S100A16 promotes differentiation and contributes to a less aggressive tumor phenotype in oral squamous cell carcinoma. BMC Cancer. 2015;15:631. doi:10.1186/s12885-015-1622-1.
  • Samal, SK, et al. Ketorolac salt is a newly discovered DDX3 inhibitor to treat oral cancer. Sci Rep. 2015;5:9982. doi:10.1038/srep09982.
  • Rheinwald, JG and Beckett, MA. Tumorigenic keratinocyte lines requiring anchorage and fibroblast support cultured from human squamous cell carcinomas. Cancer Res. 1981;41(5):1657–63.
  • Otsuka, Y, et al. High expression of EPB41L5, an integral component of the Arf6-driven mesenchymal program, correlates with poor prognosis of squamous cell carcinoma of the tongue. Cell Commun Signal. 2016;14(1):28. doi:10.1186/s12964-016-0151-0.
  • Kadletz, L, et al. AZD5582, an IAP antagonist that leads to apoptosis in head and neck squamous cell carcinoma cell lines and is eligible for combination with irradiation. Acta Otolaryngol. 2016; 137(3):320–325. doi:10.1080/00016489.2016.1242776.
  • McGregor, F, et al. Molecular changes associated with oral dysplasia progression and acquisition of immortality: potential for its reversal by 5-azacytidine. Cancer Res. 2002;62(16):4757–66.
  • Colley, HE, et al. Development of tissue-engineered models of oral dysplasia and early invasive oral squamous cell carcinoma. Br J Cancer. 2011;105(10):1582–92. doi:10.1038/bjc.2011.403.
  • Gaballah, K, et al. Tissue engineering of oral dysplasia. J Pathol. 2008;215(3):280–9. doi:10.1002/path.2360.
  • Gaballah, K, et al. Lysis of Dysplastic but not Normal Oral Keratinocytes and Tissue-Engineered Epithelia with Conditionally Replicating Adenoviruses. Cancer Res. 2007;67(15):7284–94. doi:10.1158/0008-5472.CAN-06-3834.
  • Mian, SA, et al. Raman spectroscopy can discriminate between normal, dysplastic and cancerous oral mucosa: a tissue-engineering approach. J Tissue Eng Regen Med. 2016; 11(11):3253–3262. doi:10.1002/term.2234.
  • Chang, SE, et al. DOK, a cell line established from human dysplastic oral mucosa, shows a partially transformed non-malignant phenotype. Int J Cancer. 1992;52(6):896–902. doi:10.1002/ijc.2910520612.
  • Kulasekara, KK, et al. Cancer progression is associated with increased expression of basement membrane proteins in three-dimensional in vitro models of human oral cancer. Arch Oral Biol. 2009;54(10):924–31. doi:10.1016/j.archoralbio.2009.07.004.
  • Rajendiran, S, et al. MIEN1 promotes oral cancer progression and implicates poor overall survival. Cancer Biol Ther. 2015;16(6):876–85. doi:10.1080/15384047.2015.1040962.
  • Dalley, AJ, et al. Organotypic culture of normal, dysplastic and squamous cell carcinoma-derived oral cell lines reveals loss of spatial regulation of CD44 and p75 NTR in malignancy. J Oral Pathol Med. 2013;42(1):37–46. doi:10.1111/j.1600-0714.2012.01170.x.
  • Chan LP, et al. IL-8 promotes HNSCC progression on CXCR1/2-meidated NOD1/RIP2 signaling pathway. Oncotarget. 2016; 7(38):61820–61831. doi:10.18632/oncotarget.11445.
  • Dong Y, et al. Establishment of a new OSCC cell line derived from OLK and identification of malignant transformation-related proteins by differential proteomics approach. Sci Rep. 2015;5:12668. doi:10.1038/srep12668.
  • Rikimaru, K, et al. Growth of the malignant and nonmalignant human squamous cells in a protein-free defined medium. In Vitro Cell Dev Biol. 1990;26(9):849–56. doi:10.1007/BF02624609.
  • Harada, K, et al. Metformin in combination with 5-fluorouracil suppresses tumor growth by inhibiting the Warburg effect in human oral squamous cell carcinoma. Int J Oncol. 2016;49(1):276–84. doi:10.3892/ijo.2016.3523.
  • Pal, SK, et al. THBS1 is induced by TGFB1 in the cancer stroma and promotes invasion of oral squamous cell carcinoma. J Oral Pathol Med. 2016;45(10):730–9. doi:10.1111/jop.12430.
  • Ketkaew, Y, et al. Apigenin inhibited hypoxia induced stem cell marker expression in a head and neck squamous cell carcinoma cell line. Arch Oral Biol. 74:69–74. doi:10.1016/j.archoralbio.2016.11.010.
  • Momose, F, et al. Variant sublines with different metastatic potentials selected in nude mice from human oral squamous cell carcinomas. J Oral Pathol Med. 1989;18(7):391–5. doi:10.1111/j.1600-0714.1989.tb01570.x.
  • Yuan, Z, et al. Overexpression of HOXB7 protein reduces sensitivity of oral cancer cells to chemo-radiotherapy. Cancer Gene Ther. 2016;23:12:419–24. doi:10.1038/cgt.2016.55.
  • Kaneko, T, et al. Hypoxia-induced epithelial-mesenchymal transition is regulated by phosphorylation of GSK3-β via PI3 K/Akt signaling in oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016;122(6):719–s730. doi:10.1016/j.oooo.2016.06.008.
  • Yokoi, T, Homma, H, Odajima, T. Establishment and characterization of OSC-19 cell line in serum and protein free culture. Tumor Res. 1988;24:1–17.
  • Shibata, A, et al. Synthetic terrein inhibits progression of head and neck cancer by suppressing angiogenin production. Anticancer Res. 2016;36(5):2161–8.
  • Kawasaki, G, et al. Overexpression of metastasis-associated MTA1 in oral squamous cell carcinomas: correlation with metastasis and invasion. Int J Oral Maxillofac Surg. 2008;37(11):1039–46. doi:10.1016/j.ijom.2008.05.020.
  • Kamino, Y, et al. HBD-2 is downregulated in oral carcinoma cells by DNA hypermethylation, and increased expression of hBD-2 by DNA demethylation and gene transfection inhibits cell proliferation and invasion. Oncol Rep. 2014;32(2):462–s8. doi:10.3892/or.2014.3260.
  • Kitahara, H, et al. Eribulin sensitizes oral squamous cell carcinoma cells to cetuximab via induction of mesenchymal-to-epithelial transition. Oncol Rep. 2016;36(6);3139–44. doi:10.3892/or.2016.5189.
  • Yokoi, T, et al. Some properties of a newly established human cell line derived from an oral squamous carcinoma. Tumor Res. 1990;25(93):91–93.
  • Todoroki, K, et al. CD44v3+/CD24- cells possess cancer stem cell-like properties in human oral squamous cell carcinoma. Int J Oncol. 2016;48(1):99–109. doi:10.3892/ijo.2015.3261.
  • Urade, M, et al. Establishment of human squamous carcinoma cell lines highly and minimally sensitive to bleomycin and analysis of factors involved in the sensitivity. Cancer. 1992;69(10):2589–97. doi:10.1002/1097-0142(19920515)69:10%3c2589:: AID-CNCR2820691032%3e3.0.CO;2-Y.
  • Yazama, H, et al. Dietary glucosylceramides suppress tumor growth in a mouse xenograft model of head and neck squamous cell carcinoma by the inhibition of angiogenesis through an increase in ceramide. Int J Clin Oncol. 2015;20(3):438–46. doi:10.1007/s10147-014-0734-y.
  • Tamura, T, et al. Zoledronic acid, a third-generation bisphosphonate, inhibits cellular growth and induces apoptosis in oral carcinoma cell lines. Oncol Rep. 2011;25(4):1139–43. doi:10.3892/or.2011.1152.
  • Kitano, H, et al. Long-term gene therapy with Del1 fragment using nonviral vectors in mice with explanted tumors. Onco Targets Ther. 2016;9:503–16.
  • Berndt, A, et al. Oral squamous cell carcinoma invasion is associated with a laminin-5 matrix re-organization but independent of basement membrane and hemidesmosome formation. clues from an in vitro invasion model. Invasion Metastasis. 1997;17(5):251–8.
  • Palmerini, CA, et al. Synthesis of new indole-based bisphosphonates and evaluation of their chelating ability in PE/CA-PJ15 cells. Eur J Med Chem. 2015;102:403–12. doi:10.1016/j.ejmech.2015.08.019.
  • Lopez Jornet, P, et al. Zoledronic acid and irradiation in oral squamous cell carcinoma. J Oral Pathol Med. 2015;44(2):103–8. doi:10.1111/jop.12205.
  • Büttner, R, et al. Myofibroblasts have an impact on expression, dimerization and signaling of different ErbB receptors in OSCC cells. J Recept Signal Transduct Res. 2016;37(1):25–37. doi:10.3109/10799893.2016.1155066.
  • Jo, JR, Park, YK, Jang, BC. Short-term treatment with glucosamine hydrochloride specifically downregulates hypoxia-inducible factor-1α at the protein level in YD-8 human tongue cancer cells. Int J Oncol. 2014;44(5):1699–706. doi:10.3892/ijo.2014.2336.
  • Jung, CW, et al. Anti-cancer properties of glucosamine-hydrochloride in YD-8 human oral cancer cells: Induction of the caspase-dependent apoptosis and down-regulation of HIF-1α. Toxicol In Vitro. 2012;26(1):42–50. doi:10.1016/j.tiv.2011.10.005.
  • So, KY, Oh, SH. Heme oxygenase-1-mediated apoptosis under cadmium-induced oxidative stress is regulated by autophagy, which is sensitized by tumor suppressor p53. Biochem Biophys Res Commun. 2016;479(1):80–5. doi:10.1016/j.bbrc.2016.09.037.
  • Ahn, SG, et al. The anticancer mechanism of 2’-hydroxycinnamaldehyde in human head and neck cancer cells. Int J Oncol. 2015;47(5):1793–800. doi:10.3892/ijo.2015.3152.
  • Anh, TD, et al. The histone deacetylase inhibitor, Trichostatin A, induces G2/M phase arrest and apoptosis in YD-10B oral squamous carcinoma cells. Oncol Rep. 2012:27(2):455–60.
  • Yu, HJ, et al. Inhibition of myeloid cell leukemia-1: Association with sorafenib-induced apoptosis in human mucoepidermoid carcinoma cells and tumor xenograft. Head Neck. 2015;37(9):1326–35. doi:10.1002/hed.23749.
  • Kang, HJ, Jang, YJ. Selective apoptotic effect of Zelkova serrata twig extract on mouth epidermoid carcinoma through p53 activation. Int J Oral Sci. 2012;4(2):78–84. doi:10.1038/ijos.2012.14.
  • Lim, W, et al. Association between cancer stem cell-like properties and epithelial-to-mesenchymal transition in primary and secondary cancer cells. 2016;49(3):991–1000.
  • Rheinwald, JG, Beckett, MA. Defective terminal differentiation in culture as a consistent and selectable character of malignant human keratinocytes. Cell. 1980;22 (2.2):629–32. doi:10.1016/0092-8674(80)90373-6.
  • Sun, L, et al. MicroRNA-137 suppresses tongue squamous carcinoma cell proliferation, migration and invasion. Cell Prolif. 2016;49(5):628–35. doi:10.1111/cpr.12287.
  • Su, CC, et al. Cantharidin induced oral squamous cell carcinoma cell apoptosis via the JNK-Regulated mitochondria and endoplasmic reticulum stress-related rignaling pathways. PLoS One. 2016;11(12):e0168095. doi:10.1371/journal.pone.0168095.
  • Dai, D, et al. Inhibition of mTOR/eIF4E by anti-viral drug ribavirin effectively enhances the effects of paclitaxel in oral tongue squamous cell carcinoma. Biochem Biophys Res Commun. 2016;482(4):1259–1264. doi:10.1016/j.bbrc.2016.12.025.
  • Jin, L, et al. Icaritin induces mitochondrial apoptosis by up-regulating miR-124 in human oral squamous cell carcinoma cells. Biomed Pharmacother. 2016;85:287–295. doi:10.1016/j.biopha.2016.11.023.
  • Korvala, J, et al. MicroRNA and protein profiles in invasive versus non-invasive oral tongue squamous cell carcinoma cells in vitro. Exp Cell Res. 2016;350(1):9–18. doi:10.1016/j.yexcr.2016.10.015.
  • Zhang, H, et al. HMGA2 is associated with the aggressiveness of tongue squamous cell carcinoma cells. Oral Dis. 2016;23(2):255–264. doi:10.1111/odi.12608.
  • Gustafson, DL, et al. Dose scheduling of the dual VEGFR and EGFR tyrosine kinase inhibitor vandetanib (ZD6474, Zactima) in combination with radiotherapy in EGFR-positive and EGFR-null human head and neck tumor xenografts. Cancer Chemother Pharmacol. 2008;61(2):179–88. doi:10.1007/s00280-007-0460-5.
  • Bradshaw-Pierce, EL, et al. Pharmacokinetic-directed dosing of vandetanib and docetaxel in a mouse model of human squamous cell carcinoma. Mol Cancer Ther. 2008;7(9):3006–17. doi:10.1158/1535-7163.MCT-08-0370.
  • Bais, MV, Kukuruzinska, M, Trackman, PC. Orthotopic non-metastatic and metastatic oral cancer mouse models. Oral Oncol. 2015;51(5):476–82. doi:10.1016/j.oraloncology.2015.01.012.
  • Harada, K, Ferdous, T, Ueyama, Y. Gimeracil exerts radiosensitizing effects on oral squamous cell carcinoma cells in vitro and in vivo. Anticancer Res. 2016;36(11):5923–30. doi:10.21873/anticanres.11179.
  • Ohnishi, Y, et al. Lapatinib-resistant cancer cells possessing epithelial cancer stem cell properties develop sensitivity during sphere formation by activation of the ErbB/AKT/cyclin D2 pathway. Oncol Rep. 2016;36(5):3058–64. doi:10.3892/or.2016.5073.
  • Horikoshi, M, et al. A new human cell line derived from human carcinoma of the gingiva. I. Its establishment and morphological studies. Nihon Koku Geka Gakkai Zasshi. 1974;20(2):100–6. Article in Japanese.
  • Tsubaki, M, et al. The sensitivity of head and neck carcinoma cells to statins is related to the expression of their Ras expression status, and statin-induced apoptosis is mediated via suppression of the Ras/ERK and Ras/mTOR pathways. Clin Exp Pharmacol Physiol. 2016;44(2):222–234. doi:10.1111/1440-1681.12690.
  • Kudo, Y, et al. Establishment of an oral squamous cell carcinoma cell line with high invasive and p27 degradation activities from a lymph node metastasis. Oral Oncol. 2003;39(5):515–20. doi:10.1016/S1368-8375(03)00015-0.
  • Kudo, Y, et al. Establishment and characterization of a spindle cell squamous carcinoma cell line. 2006;35(8):479–83.
  • Inagaki, T, et al. treatment, Establishment of human oral-cancer cell lines (KOSC-2 and -3) carrying p53 and c-myc abnormalities by geneticin. Int J Cancer. 1994;56(2):301–8. doi:10.1002/ijc.2910560226.
  • Maemoto, S, et al. Mutational analysis of HRAS and KRAS genes in oral carcinoma cell lines. Odontology. 2012;100(2):149–55. doi:10.1007/s10266-011-0032-3.
  • Oyama, G, et al. Single nucleotide polymorphisms of mucosa-associated lymphoid tissue 1 in oral carcinoma cells and gingival fibroblasts. Odontology. 2013;101(2):150–5. doi:10.1007/s10266-012-0079-9.
  • Uozumi, M, et al. Induction of S100A4 gene expression inhibits in vitro invasiveness of human squamous cell carcinoma, KOSC-3 cells. Cancer Lett. 2000;149(1–2):135–41. doi:10.1016/S0304-3835(99)00352-3.
  • Chiu, KC, et al. Polarization of tumor-associated macrophages and Gas6/Axl signaling in oral squamous cell carcinoma. Oral Oncol. 2015;51(7):683–9. doi:10.1016/j.oraloncology.2015.04.004.
  • Yu, XD, et al. Resveratrol inhibits oral squamous cell carcinoma through induction of apoptosis and G2/M phase cell cycle arrest. Tumour Biol. 2016;37(3):2871–7. doi:10.1007/s13277-015-3793-4.
  • Yang, CY, Meng, CL. Regulation of PG synthase by EGF and PDGF in human oral, breast, stomach, and fibrosarcoma cancer cell lines. J Dent Res. 1994;73(8):1407–15. doi:10.1177/00220345940730080301.
  • Tu, HP, et al. Cyclosporine A enhances apoptosis in gingival keratinocytes of rats and in OECM1 cells via the mitochondrial pathway. J Periodontal Res. 2009;44:6. doi:10.1111/j.1600-0765.2008.01189.x.
  • Chang, KP, et al. Overexpression of caldesmon is associated with lymph node metastasis and poorer prognosis in patients with oral cavity squamous cell carcinoma. Cancer. 2013;119(22):4003–11. doi:10.1002/cncr.28300.
  • Chiang, CH, et al. Proteomics Analysis Reveals Involvement of Krt17 in Areca Nut-Induced Oral Carcinogenesis. J Proteome Res. 2016;15(9):2981–97. doi:10.1021/acs.jproteome.6b00138.
  • Shirako, Y, et al. Heterogeneous tumor stromal microenvironments of oral squamous cell carcinoma cells in tongue and nodal metastatic lesions in a xenograft mouse model. J Oral Pathol Med. 2015;44(9):656–68. doi:10.1111/jop.12318.
  • Dickson, MA, et al. Human keratinocytes that express hTERT and also bypass a p16(INK4a)-enforced mechanism that limits life span become immortal yet retain normal growth and differentiation characteristics. Mol Cell Biol. 2000;20(4):1436–47. doi:10.1128/MCB.20.4.1436-1447.2000.
  • Dalley, AJ, et al. Expression of ABCG2 and Bmi-1 in oral potentially malignant lesions and oral squamous cell carcinoma. Cancer Med. 2014;3(2):273–83. doi:10.1002/cam4.182.
  • Saito, Y, et al. ALY as a potential contributor to metastasis in human oral squamous cell carcinoma. J Cancer Res Clin Oncol. 2013;139(4):585–94. doi:10.1007/s00432-012-1361-5.
  • Roblegg, E, et al. Evaluation of a physiological in vitro system to study the transport of nanoparticles through the buccal mucosa. Nanotoxicology. 2012;6(4):399–413. doi:10.3109/17435390.2011.580863.
  • Konopka, K, et al. Correlation between the levels of survivin and survivin promoter-driven gene expression in cancer and non-cancer cells. Cell Mol Biol Lett. 2009;14(1):70–89. doi:10.2478/s11658-008-0034-5.
  • Best, M, et al. Characterisation and cytotoxic screening of metal oxide nanoparticles putative of interest to oral healthcare formulations in non-keratinised human oral mucosa cells in vitro. Toxicol In Vitro. 2015;30(1.B):402–11. doi:10.1016/j.tiv.2015.09.022.
  • Gokulan, R, Halagowder, D. Expression pattern of Notch intracellular domain (NICD) and Hes-1 in preneoplastic and neoplastic human oral squamous epithelium: their correlation with c-Myc, clinicopathological factors and prognosis in Oral cancer. Med Oncol. 2014;31:8. doi:10.1007/s12032-014-0126-1.
  • Pring, M, et al. Dysregulated TGF-beta1-induced Smad signalling occurs as a result of defects in multiple components of the TGF-beta signalling pathway in human head and neck carcinoma cell lines. Int J Oncol. 2006;28:5.
  • Ravindran, G, et al. Association of differential β-catenin expression with Oct- 4and Nanog in oral squamous cell carcinoma and their correlation with clinicopathological factors and prognosis. Head Neck. 2015;37(7):982–93. doi:10.1002/hed.23699.
  • O’Neill, ID. Continued misrepresentation of KB cells as being of oral cancer phenotype requires action. Oral Oncol. 2009;45(10):e117–8. doi:10.1016/j.oraloncology.2009.02.005.
  • Eagle, H. Propagation in a fluid medium of a human epidermoid carcinoma, strain KB. Proc Soc Exp Biol Med. 1955;89(3):362–4. doi:10.3181/00379727-89-21811.
  • Karthikeyan, S, et al. Glaucarubinone sensitizes KB cells to paclitaxel by inhibiting ABC transporters via ROS-dependent and p53-mediated activation of apoptotic signaling pathways. Oncotarget. 2016;7(27):42353–73. doi:10.18632/oncotarget.9865.
  • Li, LK, et al. Goniothalamin induces cell cycle arrest and apoptosis in H400 human oral squamous cell carcinoma: A caspase-dependent mitochondrial-mediated pathway with downregulation of NF-κβ. Arch Oral Biol. 2016;64:28–38. doi:10.1016/j.archoralbio.2015.12.002.
  • Khan, E, et al. Architectural characterization of organotypic cultures of H400 and primary rat keratinocytes. J Biomed Mater Res A. 2012;100(12):3227–38. doi:10.1002/jbm.a.34263.
  • Shaghayegh, G, et al. Cell cycle arrest and mechanism of apoptosis induction in H400 oral cancer cells in response to Damnacanthal and Nordamnacanthal isolated from Morinda citrifolia. Cytotechnology. 2016;68(5):1999–2013. doi:10.1007/s10616-016-0014-y.
  • Lourenço, SV, et al. Establishment and characterization of an oral mucosal melanoma cell line (MEMO) derived from a longstanding primary oral melanoma. Am J Dermatopathol. 2013;35(2):248–51. doi:10.1097/DAD.0b013e31826a9905.
  • Zhao, M, et al. Assembly and initial characterization of a panel of 85 genomically validated cell lines from diverse head and neck tumor sites. Clin Cancer Res. 2011;17(23):7248–64. doi:10.1158/1078-0432.CCR-11-0690.
  • Sacks, PG, et al. Establishment and characterization of two new squamous cell carcinoma cell lines derived from tumors of the head and neck. Cancer Res. 1988;48(10):2858–66.
  • Xi, S, et al. Decreased STAT1 expression by promoter methylation in squamous cell carcinogenesis. J Natl Cancer Inst. 2006;98(3):181–9. doi:10.1093/jnci/djj020.
  • Zweifel, BS, et al. Direct evidence for a role of cyclooxygenase 2-derived prostaglandin E2 in human head and neck xenograft tumors. Cancer Res. 2002;62:(22):6706–11.
  • Li, C, et al. Dasatinib blocks cetuximab- and radiation-induced nuclear translocation of the epidermal growth factor receptor in head and neck squamous cell carcinoma. Radiother Oncol. 2010;97(2):330–7. doi:10.1016/j.radonc.2010.06.010.
  • Rangan, SR. A new human cell line (FaDu) from a hypopharyngeal carcinoma. Cancer. 1972;29(1):117–21. doi:10.1002/1097-0142(197201)29:1%3c117:: AID-CNCR2820290119%3e3.0.CO;2-R.
  • Schneider, S, et al. Effects of neratinib and combination with irradiation and chemotherapy in head and neck cancer cells. Oral Dis. 2016;22(8):797–804. doi:10.1111/odi.12552.
  • Yang, SW, et al. MART-10, a newly synthesized vitamin D analog, represses metastatic potential of head and neck squamous carcinoma cells. Drug Des Devel Ther. 2016;10:1995–2002.
  • Chiu YW, et al. Tyrosine 397 phosphorylation is critical for FAK-promoted Rac1 activation and invasive properties in oral squamous cell carcinoma cells. Lab Invest. 2016;96(3):296–306. doi:10.1038/labinvest.2015.151.
  • Kawamata H, et al. Possible contribution of active MMP2 to lymph-node metastasis and secreted cathepsin L to bone invasion of newly established human oral-squamous-cancer cell lines. Int J Cancer. 1997;70(1):120–7. doi:10.1002/(SICI)1097-0215(19970106)70:1%3c120:: AID-IJC18%3e3.0.CO;2-P.
  • Tada T, et al. Oral squamous cell carcinoma cells modulate osteoclast function by RANKL-dependent and -independent mechanisms. Cancer Lett. 2009;274(1):126–31. doi:10.1016/j.canlet.2008.09.015.
  • Erdem NF, Carlson ER, Gerard DA. Characterization of gene expression profiles of 3 different human oral squamous cell carcinoma cell lines with different invasion and metastatic capacities. J Oral Maxillofac Surg. 2008;66(5):918–27. doi:10.1016/j.joms.2007.12.036.
  • Kraus D, et al. Ghrelin promotes oral tumor cell proliferation by modifying GLUT1 expression. Cell Mol Life Sci. 2016;73(6):1287–99. doi:10.1007/s00018-015-2048-2.
  • Harada K, et al. Induction of artificial cancer stem cells from tongue cancer cells by defined reprogramming factors. BMC Cancer. 2016;16, 548. doi:10.1186/s12885-016-2416-9.
  • Ishisaki A, et al. Identification and characterization of autocrine-motility-factor-like activity in oral squamous-cell-carcinoma cells. Int J Cancer. 1994;59(6):783–8. doi:10.1002/ijc.2910590613.
  • Nguyen PT, et al. The FGFR1 inhibitor PD173074 induces mesenchymal-epithelial transition through the transcription factor AP-1. Br J Cancer. 2013;109(8):2248–58. doi:10.1038/bjc.2013.550.
  • Sakha S, et al. Exosomal microRNA miR-1246 induces cell motility and invasion through the regulation of DENND2D in oral squamous cell carcinoma. Sci Rep. 2016;6:38750. doi:10.1038/srep38750.
  • Heo DS, et al. Biology, cytogenetics, and sensitivity to immunological effector cells of new head and neck squamous cell carcinoma lines. Cancer Res. 1989;49(18):5167–75.
  • Minhas KM, et al. Spindle assembly checkpoint defects and chromosomal instability in head and neck squamous cell carcinoma. Int J Cancer. 2003;107(1):46–52. doi:10.1002/ijc.11341.
  • Brenner JC, et al. Genotyping of 73 UM-SCC head and neck squamous cell carcinoma cell lines. Head Neck. 2010;32(4):417–26.
  • Dickman CT, et al. Molecular characterization of immortalized normal and dysplastic oral cell lines. J Oral Pathol Med. 2015;44(5):329–36. doi:10.1111/jop.12236.
  • Hansson A, et al. Analysis of proliferation, apoptosis and keratin expression in cultured normal and immortalized human buccal keratinocytes. Eur J Oral Sci. 2003;111(1):34–41. doi:10.1034/j.1600-0722.2003.00010.x.
  • Gröger S, Michel J, Meyle J. Establishment and characterization of immortalized human gingival keratinocyte cell lines. J Periodontal Res. 2008;43(6):604–14. doi:10.1111/j.1600-0765.2007.01019.x.
  • Gröger S, et al. Effects of Porphyromonas gingivalis infection on human gingival epithelial barrier function in vitro. Eur J Oral Sci. 2010;118(6):582–9. doi:10.1111/j.1600-0722.2010.00782.x.
  • Gröger S, et al. Influence of retinoic acid on human gingival epithelial barriers. J Periodontal Res. 2016;51(6):748–57. doi:10.1111/jre.12351.
  • Hatakeyama S, et al. Establishment of gingival epithelial cell lines from transgenic mice harboring temperature sensitive simian virus 40 large T-antigen gene. J Oral Pathol Med. 2001;30(5):296–304. doi:10.1034/j.1600-0714.2001.300507.x.
  • Hatakeyama S, Ishida K, Takeda Y. Changes in cell characteristics due to retinoic acid; specifically, a decrease in the expression of claudin-1 and increase in claudin-4 within tight junctions in stratified oral keratinocytes. J Periodontal Res. 2010;45(2):207–15. doi:10.1111/j.1600-0765.2009.01219.x.
  • Hatakeyama S, et al. Expression of connexins and the effect of retinoic acid in oral keratinocytes. J Oral Sci. 2011;53(3):327–32. doi:10.2334/josnusd.53.327.
  • Hatakeyama S, et al. Retinoic acid disintegrated desmosomes and hemidesmosomes in stratified oral keratinocytes. J Oral Pathol Med. 2004;33(10):622–8. doi:10.1111/j.1600-0714.2004.00245.x.
  • Damek-Poprawa M, et al. Cell junction remodeling in gingival tissue exposed to a microbial toxin. J Dent Res. 2013;92(6):518–23. doi:10.1177/0022034513486807.
  • Li S, et al. P. gingivalis modulates keratinocytes through FOXO transcription factors. PLoS One. 2013;8:11.
  • Dickinson BC, et al. Interaction of oral bacteria with gingival epithelial cell multilayers. Mol Oral Microbiol. 2011;26(3):210–20. doi:10.1111/j.2041-1014.2011.00609.x.
  • Katz J, et al. Characterization of Porphyromonas gingivalis-induced degradation of epithelial cell junctional complexes. Infect Immun. 2000;68(3):1441–9. doi:10.1128/IAI.68.3.1441-1449.2000.
  • Meyle J, et al. Transepithelial electrical resistance and tight junctions of human gingival keratinocytes. J Periodontal Res. 1999;34(4):214–22. doi:10.1111/j.1600-0765.1999.tb02244.x.
  • Belibasakis GN, et al. The expression of gingival epithelial junctions in response to subgingival biofilms. Virulence. 2015;6(7):704–9. doi:10.1080/21505594.2015.1081731.
  • Ilmarinen T, et al. Towards a defined, serum- and feeder-free culture of stratified human oral mucosal epithelium for ocular surface reconstruction. Acta Ophthalmol. 2013;91(8):744–50. doi:10.1111/j.1755-3768.2012.02523.x.
  • Shimazaki J, et al. Barrier function of cultivated limbal and oral mucosal epithelial cell sheets. Invest Ophthalmol Vis Sci. 2009;50(12):5672–80. doi:10.1167/iovs.09-3820.
  • Kimura T, et al. Transport of D-glucose across cultured stratified cell layer of human oral mucosal cells. JPP. 2002;(54):213–9. doi:10.1211/0022357021778402.
  • Iida T, et al. Development of a tissue-engineered human oral mucosa equivalent based on an acellular allogeneic dermal matrix: a preliminary report of clinical application to burn wounds. Scand J Plast Reconstr Surg Hand Surg. 2005;39( 3):138–46. doi:10.1080/0284431051006376.
  • Nakamura T, Kinoshita S. Ocular surface reconstruction using cultivated mucosal epithelial stem cells. Cornea. 2003;22(7 Suppl):S75–80. doi:10.1097/00003226-200310001-00011.
  • Dobrowolski D, et al. Cultivated oral mucosa epithelium in ocular surface reconstruction in aniridia patients. Biomed Res Int. 2015;2015, 281870. doi:10.1155/2015/281870.
  • Bhargava S, et al. Tissue-engineered buccal mucosa urethroplasty-clinical outcomes. Eur Urol. 2008;53(6):1263–9. doi:10.1016/j.eururo.2008.01.061.
  • Xie M, et al. Tissue-engineered buccal mucosa using silk fibroin matrices for urethral reconstruction in a canine model. J Surg Res. 2014;188(1):1–7. doi:10.1016/j.jss.2013.11.1102.
  • Moharamzadeh K, et al. Tissue-engineered oral mucosa: a review of the scientific literature. J Dent Res. 2007;86(2):115–24. doi:10.1177/154405910708600203.
  • Moharamzadeh K, et al. Tissue-engineered oral mucosa. J Dent Res. 2012;91(7):642–50. doi:10.1177/0022034511435702.
  • Kinikoglu B, Damour O, Hasirci V. Tissue Engineering of Oral Mucosa: A Shared Concept With Skin. Journal of Artificial Organs. 2015;18(1):8–19. doi:10.1007/s10047-014-0798-5.
  • Nor NH, et al. Properties of cell sources in tissue-engineered three dimensional oral mucosa model: A Review. Curr Stem Cell Res Ther. 2017;12(1):52–60.
  • Kosten IJ, et al. MUTZ-3 Langerhans cell maturation and CXCL12 independent migration in reconstructed human gingiva. ALTEX. 2016;33(4):423–34.
  • Heller M, et al. Tissue engineered pre-vascularized buccal mucosa equivalents utilizing a primary triculture of epithelial cells, endothelial cells and fibroblasts. Biomaterials. 2016;77:207–15. doi:10.1016/j.biomaterials.2015.10.073.
  • Dongari-Bagtzoglou A, Kashleva H. Development of a highly reproducible three-dimensional organotypic model of the oral mucosa. Nat Protoc. 2006;1(4):2012–8. doi:10.1038/nprot.2006.323.
  • Ceder R, et al. Differentiation-promoting culture of competent and noncompetent keratinocytes identifies biomarkers for head and neck cancer. Am J Pathol. 2012;180(2):457–72. doi:10.1016/j.ajpath.2011.10.016.
  • Chakravarti N, et al. Differential inhibition of protein translation machinery by curcumin in normal, immortalized, and malignant oral epithelial cells. Cancer Prev Res (Phila). 2010;3(3):331–8. doi:10.1158/1940-6207.CAPR-09-0076.
  • Parikh N, et al. Isolation and characterization of an immortalized oral keratinocyte cell line of mouse origin. Arch Oral Biol. 2008;53(11):1091–100. doi:10.1016/j.archoralbio.2008.07.002.
  • Conti HR, et al. IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis. Cell Host & Microbe. 2016;20(5):606–17. doi:10.1016/j.chom.2016.10.001.
  • Takahashi C, et al. Newly established cell lines from mouse oral epithelium regenerate teeth when combined with dental mesenchyme. In Vitro Cell Dev Biol Anim. 2010;46(5):457–68. doi:10.1007/s11626-009-9265-7.
  • Mäkelä M, Salo T, Larjava H. MMP-9 from TNF alpha-stimulated keratinocytes binds to cell membranes and type I collagen: a cause for extended matrix degradation in inflammation? Biochem Biophys Res Commun. 1998;253(2):325–35. doi:10.1006/bbrc.1998.9641.
  • Hildebrand HC, et al. Characterization of organotypic keratinocyte cultures on de-epithelialized bovine tongue mucosa. Histol Histopathol. 2002;17(1):151–63.
  • Turunen A, et al. The combined effects of irradiation and herpes simplex virus type 1 infection on an immortal gingival cell line. Virol J. 2014;11, 125. doi:10.1186/1743-422X-11-125.
  • Turunen A, Syrjänen S. Extracellular calcium regulates keratinocyte proliferation and HPV 16 E6 RNA expression in vitro. APMIS. 2014;122(9):781–9. doi:10.1111/apm.12227.
  • Gursoy UK, et al. Construction and characterization of a multilayered gingival keratinocyte culture model: the TURK-U model. Cytotechnology. 2016;68(6):2345–54. doi:10.1007/s10616-016-0029-4.
  • Oda D, et al. HPV immortalization of human oral epithelial cells: a model for carcinogenesis. Exp Cell Res. 1996;226(1):164–9. doi:10.1006/excr.1996.0215.
  • Parikka M, et al. Alterations of collagen XVII expression during transformation of oral epithelium to dysplasia and carcinoma. J Histochem Cytochem. 2003;51(7):921–9. doi:10.1177/002215540305100707.
  • Lee HJ, et al. Effects of nicotine on proliferation, cell cycle, and differentiation in immortalized and malignant oral keratinocytes. J Oral Pathol Med. 2005;34(7):436–43. doi:10.1111/j.1600-0714.2005.00342.x.
  • Roesch-Ely M, et al. Organotypic co-cultures allow for immortalized human gingival keratinocytes to reconstitute a gingival epithelial phenotype in vitro. Differentiation. 2006;74(9–10):622–37. doi:10.1111/j.1432-0436.2006.00099.x.
  • Buskermolen JK, et al. Development of a full-thickness human gingiva equivalent constructed from immortalized keratinocytes and fibroblasts. Tissue Eng Part C Methods. 2016;22(8):781–91. doi:10.1089/ten.tec.2016.0066.
  • Kibe T, et al. Immortalization and characterization of normal oral epithelial cells without using HPV and SV40 genes. Oral Science International. 2011;8(1):20–28. doi:10.1016/S1348-8643(11)00009-7.
  • Miyata K, Takebe J. Anodized-hydrothermally treated titanium with a nanotopographic surface structure regulates integrin-α6β4 and laminin-5 gene expression in adherent murine gingival epithelial cells. J Prosthodont Res. 2013;57(2):99–108. doi:10.1016/j.jpor.2012.12.002.
  • Nakayama Y, et al. Amelotin gene expression is temporarily being upregulated at the initiation of apoptosis induced by TGFβ1 in mouse gingival epithelial cells. Apoptosis. 2016;21(10):1057–70. doi:10.1007/s10495-016-1279-5.
  • Moffatt-Jauregui, CE, et al. Establishment and characterization of a telomerase immortalized human gingival epithelial cell line. J Periodontal Res. 2013;48(6):713–21.
  • Jauregui, CE, et al. Suppression of T-Cell Chemokines by Porphyromonas gingivalis. Infect Immun. 2013;81(7):2288–95. doi:10.1128/IAI.00264-13.
  • Takeuchi, H, et al. The serine phosphatase SerB of Porphyromonas gingivalis suppresses IL-8 production by dephosphorylation of NF-κB RelA/p65. PLoS Pathog. 2013;9(4):e1003326. doi:10.1371/journal.ppat.1003326.
  • Wang, H, et al. Porphyromonas gingivalis-induced reactive oxygen species activate JAK2 and regulate production of inflammatory cytokines through c-Jun. Infect Immun. 2014;82(10):4118–26. doi:10.1128/IAI.02000-14.
  • Chen, SC, et al. MicroRNAs regulate cytokine responses in gingival epithelial cells. Infect Immun. 2016;84(12):3282–9. doi:10.1128/IAI.00263-16.
  • Bao, K, Akguel, B, Bostanci, N. Establishment and characterization of immortalized gingival epithelial and fibroblastic cell lines for the development of organotypic cultures. Cells Tissues Organs. 2014;199(4):228–37. doi:10.1159/000363694.
  • Kubo, C, et al. Immortalization of normal human gingival keratinocytes and cytological and cytogenetic characterization of the cells. Odontology. 2009;97(1):18–31. doi:10.1007/s10266-008-0089-9.
  • Kusumoto, Y, et al. Human gingival epithelial cells produce chemotactic factors interleukin-8 and monocyte chemoattractant protein-1 after stimulation with Porphyromonas gingivalis via toll-like receptor 2. J Periodontol. 2004;75(3):370–9. doi:10.1902/jop.2004.75.3.370.
  • Umeda, JE, et al. Differential transcription of virulence genes in Aggregatibacter actinomycetemcomitans serotypes. J Oral Microbiol. 2013;5. doi:10.3402/jom.v5i0.21473.
  • Savitri, IJ, et al. Irsogladine maleate inhibits Porphyromonas gingivalis-mediated expression of toll-like receptor 2 and interleukin-8 in human gingival epithelial cells. J Periodontal Res. 2015;50(4):486–93. doi:10.1111/jre.12231.
  • Ouhara, K, et al. miR-584 expressed in human gingival epithelial cells is induced by Porphyromonas gingivalis stimulation and regulates interleukin-8 production via lactoferrin receptor. J Periodontol. 85, 2014;6:e198–204. doi:10.1902/jop.2013.130335.
  • Benso, B, et al. Malva sylvestris inhibits inflammatory response in oral human cells. An In Vitro Infection Model. PLoS One. 2015;10(10):e0140331. doi:10.1371/journal.pone.0140331.
  • Castilho, et al. Rac1 is required for epithelial stem cell function during dermal and oral mucosal wound healing but not for tissue homeostasis in mice. 2010;5(5):e10503.
  • Glazer, CA, et al. The Role of MAGEA2 in head and neck cancer. Arch Otolaryngol Head Neck Surg. 2011;137(3):286–93. doi:10.1001/archoto.2011.2.
  • Bhan, S, et al. MAGEA4 induces growth in normal oral keratinocytes by inhibiting growth arrest and apoptosis. Oncol Rep. 2012;28(4):1498–502. doi:10.3892/or.2012.1934.
  • Pellicioli, AC, et al. Laser phototherapy accelerates oral keratinocyte migration through the modulation of the mammalian target of rapamycin signaling pathway. J Biomed Opt. 2014;19(2):028002. doi:10.1117/1.JBO.19.2.028002.
  • Martins, MD, et al. Epigenetic modifications of histones in periodontal disease. J Dent Res. 2016;95(2):215–22. doi:10.1177/0022034515611876.
  • Dongari-Bagtzoglou, A, Kashleva, H. Candida albicans triggers interleukin-8 secretion by oral epithelial cells. Microb Pathog. 2003;34(4):169–77. doi:10.1016/S0882-4010(03)00004-4.
  • Wöllert, T, et al. Human oral keratinocytes: a model system to analyze host-pathogen interactions. Methods Mol Biol. 2012;845:289–302. doi:10.1007/978-1-61779-539-8_19.
  • Volk, et al. Glutathione level and genotoxicity in human oral keratinocytes exposed to TEGDMA. J Biomed Mater Res B Appl Biomater. 2012;100( 2):391–9. doi:10.1002/jbm.b.31960.
  • Ramage, G, et al. Antifungal, cytotoxic, and immunomodulatory properties of tea tree oil and its derivative components: potential role in management of oral candidosis in cancer patients. Front Microbiol. 2012;3:220. doi:10.3389/fmicb.2012.00220.
  • Millhouse, E, et al. Development of an in vitro periodontal biofilm model for assessing antimicrobial and host modulatory effects of bioactive molecules. BMC Oral Health. 2014;14:80. doi:10.1186/1472-6831-14-80.
  • Wessels, M, et al. Genotoxic effects of camphorquinone and DMT on human oral and intestinal cells. Dent Mater. 2015;31(10):1159–68. doi:10.1016/j.dental.2015.06.007.
  • Almela, T, Brook, IM, Moharamzadeh, K. Development of three-dimensional tissue engineered bone-oral mucosal composite models. J Mater Sci Mater Med. 2016;27:65. doi:10.1007/s10856-016-5676-7.
  • Gilchrist, EP, et al. Establishment of a human polyclonal oral epithelial cell line. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000;90(3):340–7. doi:10.1067/moe.2000.107360.
  • Kanno, F, Korostoff J, Volgina A, DiRienzo JM. Resistance of human periodontal ligament fibroblasts to the cytolethal distending toxin of Actinobacillus actinomycetemcomitans. J Peridontol. 2005;76(7):1189–201. doi:10.1902/jop.2005.76.7.1189.
  • Feghali, K, Tanabe, S, Grenier, D. Soluble CD14 induces cytokine release by human oral epithelial cells. J Periodontal Res. 2011;46(1):147–52. doi:10.1111/j.1600-0765.2010.01311.x.
  • Yee, M, et al. Porphyromonas gingivalis stimulates IL-6 and IL-8 secretion in GMSM-K, HSC-3 and H413 oral epithelial cells. Anaerobe. 2014;28:62–7. doi:10.1016/j.anaerobe.2014.05.011.
  • Tabuchi, Y, et al. Development of oral epithelial cell line ROE2 with differentiation potential from transgenic rats harboring temperature-sensitive simian virus40 large T-antigen gene. Exp Anim. 1, 2014;63:31–44. doi:10.1538/expanim.63.31.
  • Tabuchi, Y, et al. Genes and gene networks involved in sodium fluoride-elicited cell death accompanying endoplasmic reticulum stress in oral epithelial cells. Int J Mol Sci. 2014;15(5):8959–78. doi:10.3390/ijms15058959.
  • Eirheim, HU, Bundgaard, C, Nielsen, HM. Evaluation of different toxicity assays applied to proliferating cells and to stratified epithelium in relation to permeability enhancement with glycocholate. Toxicol In Vitro. 2004;18(5):649–57. doi:10.1016/j.tiv.2004.02.003.
  • Ye, P, et al. CD24 regulated gene expression and distribution of tight junction proteins is associated with altered barrier function in oral epithelial monolayers. BMC Cell Biol. 2009;10:2. doi:10.1186/1471-2121-10-2.
  • Acheampong, EA, et al. Molecular interactions of human immunodeficiency virus type 1 with primary human oral keratinocytes. J Virol. 2005;79(13):8440–53. doi:10.1128/JVI.79.13.8440-8453.2005.
  • Schaal S, Kunsch K, Kunsch S. Der Mensch in Zahlen: Eine Datensammlung in Tabellen mit über 20000 Einzelwerten. s.l.: Springer-Verlag; 2015: 506.
  • Edgar WM. Saliva: its secretion, composition and functions. Br Dent J. 1992;172(8):305–12. doi:10.1038/sj.bdj.4807861.
  • Nelson, J, Manzella, K, Baker, OJ. Current cell models for bioengineering a salivary gland: a mini-review of emerging technologies. Oral Dis. 2013;19(3):236–44. doi:10.1111/j.1601-0825.2012.01958.x.
  • Maria, OM, et al. Distribution of tight junction proteins in adult human salivary glands. J Histochem Cytochem. 2008;56(12):1093–8. doi:10.1369/jhc.2008.951780.
  • Baker, OJ. Tight junctions in salivary epithelium. J Biomed Biotechnol. 2010;2010:278948. doi:10.1155/2010/278948.
  • Baker, OJ. Current trends in salivary gland tight junctions. Tissue Barriers. 2016;4:3. doi:10.1080/21688370.2016.1162348.
  • Zhang, GH, Wu, LL, Yu, GY. Tight junctions and paracellular fluid and ion transport in salivary glands. Chin J Dent Res. 2013;16(1):13–46.
  • Michikawa, H, Fujita-Yoshigaki, J, Sugiya, H. Enhancement of barrier function by overexpression of claudin-4 in tight junctions of submandibular gland cells. Cell Tissue Res. 2008;334(2):255–64. doi:10.1007/s00441-008-0689-2.
  • Xiang, RL, et al. Claudin-4 is required for AMPK-modulated paracellular permeability in submandibular gland cells. J Mol Cell Biol. 2014;6(6):486–97. doi:10.1093/jmcb/mju048.
  • Cong, X, et al. Claudin-4 is required for modulation of paracellular permeability by muscarinic acetylcholine receptor in epithelial cells. J Cell Sci. 2015;128(12):2271–86. doi:10.1242/jcs.165878.
  • Li, D, Mrsny, RJ. Oncogenic Raf-1 disrupts epithelial tight junctions via downregulation of occludin. J Cell Biol. 2000;148(4):791–800. doi:10.1083/jcb.148.4.791.
  • Hamm-Alvarez, SF, et al. Etk/Bmx activation modulates barrier function in epithelial cells. Am J Physiol Cell Physiol. 2001;280(6):C1657–68. doi:10.1152/ajpcell.2001.280.6.C1657.
  • Castro, R, et al. Ion transport in an immortalized rat submandibular cell line SMG-C6. Proc Soc Exp Biol Med. 2000;225(1):39–48. doi:10.1046/j.1525-1373.2000.22505.x.
  • Aframian, DJ, et al. Absence of tight junction formation in an allogeneic graft cell line used for developing an engineered artificial salivary gland. Tissue Eng. 2002;8(5):871–8. doi:10.1089/10763270260424231.
  • Maria, OM, et al. Matrigel improves functional properties of human submandibular salivary gland cell line. Int J Biochem Cell Biol. 2011;43(4):622–31. doi:10.1016/j.biocel.2011.01.001.
  • Capes-Davis, A, et al. Check your cultures! A list of cross-contaminated or misidentified cell lines. Int J Cancer. 2010;127(1):1–8. doi:10.1002/ijc.25242.
  • Uematsu, T, et al. Expression of ATP-binding cassette transporter in human salivary ducts. Arch Oral Biol. 2003;48(1):87–90. doi:10.1016/S0003-9969(02)00159-0.
  • Matsuoka T, Aiyama S, Kikuchi KI, Koike K. Uptake of cationized ferritin by the epithelium of the main excretory duct of the rat submandibular gland. Anat Rec. 2000;258(1):108–13. doi:10.1002/(SICI)1097-0185(20000101)258:1%3c108:: AID-AR12%3e3.0.CO;2-D.
  • Lotti LV, Hand AR. Endocytosis of native and glycosylated bovine serum albumin by duct cells of the rat parotid gland. Cell Tissue Res. 1989;255(2):333–42. doi:10.1007/BF00224116.
  • Park MY, Kim N, Wu LL, Yu GY, Park K. Role of flotillins in the endocytosis of GPCR in salivary gland epithelial cells. Biochem Biophys Res Commun. 2016;476(4):237–44. doi:10.1016/j.bbrc.2016.05.103.
  • Pirraglia C, Walters J, Myat MM. Pak1 control of E-cadherin endocytosis regulates salivary gland lumen size and shape. Development. 2010;137(24):4177–89. doi:10.1242/dev.048827.
  • Lisi S, Sisto M, Soleti R, Saponaro C, Scagliusi P. Fcgamma receptors mediate internalization of anti-Ro and anti-La autoantibodies from Sjögren’s syndrome and apoptosis in human salivary gland cell line A-253. J Oral Pathol Med. 2007;36(9):511–23. doi:10.1111/j.1600-0714.2007.00563.x.
  • Liu CX, Li Y, Obermoeller-McCormick LM, Schwartz AL, Bu G. The putative tumor suppressor LRP1B, a novel member of the low density lipoprotein (LDL) receptor family, exhibits both overlapping and distinct properties with the LDL receptor-related protein. J Biol Chem. 2001;276(31):28889–96. doi:10.1074/jbc.M102727200.
  • Burghartz M, Lennartz S, Schweinlin M, Hagen R, Kleinsasser N, Hackenberg S, Steußloff G, Scherzad A, Radeloff K, Ginzkey C, et al. Development of human salivary gland-like tissue in vitro. Tissue Eng Part A. 2018;24(3-4):301–309. doi:10.1089/ten.tea.2016.0466.
  • Bamforth, SD, et al. A dominant mutant of occludin disrupts tight junction structure and function. J Cell Sci. 1999;112(12):1879–88.
  • Vogel, C, et al. Flt-1, but not Flk-1 mediates hyperpermeability through activation of the PI3-K/Akt pathway. J Cell Physiol. 2007;212(1):236–43. doi:10.1002/jcp.21022.
  • Mitsui, R, et al. Maintenance of paracellular barrier function by insulin-like growth factor-I in submandibular gland cells. Arch Oral Biol. 2010;55(12):963–9. doi:10.1016/j.archoralbio.2010.07.023.
  • He X, et al. A polarized salivary cell monolayer useful for studying transepithelial fluid movement in vitro. Pflugers Arch. 1998;435(3):375–81. doi:10.1007/s004240050526.
  • Li J, et al. ZO-1 and -2 Are Required for TRPV1-Modulated Paracellular Permeability. J Dent Res. 2015;94(12):1748–56. doi:10.1177/0022034515609268.
  • Cong X, et al. Occludin is required for TRPV1-modulated paracellular permeability in the submandibular gland. J Cell Sci. 2013;126(5):1109–21. doi:10.1242/jcs.111781.
  • Ding C, et al. Adiponectin increases secretion of rat submandibular gland via adiponectin receptors-mediated AMPK signaling. PLoS One. 2013;8(5):e63878. doi:10.1371/journal.pone.0063878.
  • Quissell DO, et al. Development and characterization of SV40 immortalized rat parotid acinar cell lines. In Vitro Cell Dev Biol Anim. 1998;34(1):58–67. doi:10.1007/s11626-998-0054-5.
  • Shirasuna K, Sato M, Miyazaki T. A neoplastic epithelial duct cell line established from an irradiated human salivary gland. Cancer. 1981;48(3):745–52. doi:10.1002/1097-0142(19810801)48:3%3c745:: AID-CNCR2820480314%3e3.0.CO;2-7.
  • Sato M, et al. Search for specific markers of neoplastic epithelial duct and myoepithelial cell lines established from human salivary gland and characterization of their growth in vitro. Cancer. 1984;54(12):2959–67. doi:10.1002/1097-0142(19841215)54:12%3c2959:: AID-CNCR2820541225%3e3.0.CO;2-5.
  • Jang SI, et al. Establishment of functional acinar-like cultures from human salivary glands. J Dent Res. 2015;94(2):304–11. doi:10.1177/0022034514559251.
  • Tran SD, et al. Primary culture of polarized human salivary epithelial cells for use in developing an artificial salivary gland. Tissue Eng. 2005;11(1–2):172–81. doi:10.1089/ten.2005.11.172.
  • Hegyesi O, et al. Evidence for active electrolyte transport by two-dimensional monolayers of human salivary epithelial cells. Tissue Eng Part C Methods. 2015;21(12):1226–36. doi:10.1089/ten.tec.2014.0614.
  • Maria OM, et al. Matrigel improves functional properties of primary human salivary gland cells. Tissue Eng Part A. 2011a;17(9–10):1229–38. doi:10.1089/ten.tea.2010.0297.
  • Szlávik V, et al. Differentiation of primary human submandibular gland cells cultured on basement membrane extract. Tissue Eng Part A. 2008;14(11):1915–26. doi:10.1089/ten.tea.2007.0208.
  • Tran SD, et al. Re-engineering primary epithelial cells from rhesus monkey parotid glands for use in developing an artificial salivary gland. Tissue Eng. 2006;12(10):2939–48. doi:10.1089/ten.2006.12.2939.
  • Aframian DJ, et al. Characterization of murine autologous salivary gland graft cells: a model for use with an artificial salivary gland. Tissue Eng. 2004;10(5–6):914–20. doi:10.1089/1076327041348518.