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Immunological Investigations
A Journal of Molecular and Cellular Immunology
Volume 49, 2020 - Issue 4
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The Role of Stroma in Ovarian Cancer

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References

  • Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, Sovak MA, Yi J, Nycum LR. 2012. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 30:2039–45.
  • Andrae J, Gallini R, Betsholtz C. 2008. Role of platelet-derived growth factors in physiology and medicine. Genes Dev. 22:1276–312.
  • Anggorowati N, Ratna Kurniasari C, Damayanti K, Cahyanti T, Widodo I, Ghozali A, Romi MM, Sari DC, Arfian N. 2017. Histochemical and immunohistochemical study ofα-SMA, collagen, and PCNA in epithelial ovarian neoplasm. Asian Pac J Cancer Prev. 18:667–71.
  • Anttila MA, Tammi RH, Tammi MI, Syrjänen KJ, Saarikoski SV, Kosma VM. 2000. High levels of stromal hyaluronan predict poor disease outcome in epithelial ovarian cancer. Cancer Res. 1; 60(1):150–55.
  • Armulik A, Genové G, Betsholtz C. 2011. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell. 21:193–215.
  • Attieh Y, Clark AG, Grass C, Richon S, Pocard M, Mariani P, Elkhatib N, Betz T, Gurchenkov B, Vignjevic DM. 2017. Cancer-associated fibroblasts lead tumor invasion through integrin-β3-dependent fibronectin assembly. J Cell Biol. 216:3509–20.
  • Augsten M. 2014. Cancer-associated fibroblasts as another polarized cell type of the tumor microenvironment. Front Oncol. 4:62.
  • Bae S, Park CW, Son HK, Ju HK, Paik D, Jeon CJ, Koh GY, Kim J, Kim H. 2008. Fibroblast activation protein alpha identifies mesenchymal stromal cells from human bone marrow. Br J Haematol. 142:827–30.
  • Balkwill F, Mantovani A. 2001. Inflammation and cancer: back to Virchow? Lancet. 357:539–45.
  • Berkenblit A, Cannistra SA. 2005. Advances in the management of epithelial ovarian cancer. J Reprod Med. 50:426–38.
  • Bingle L, Brown NJ, Lewis CE. 2002. The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol. 196:254–65.
  • Bissell MJ, Hines WC. 2011. Why don’t we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nat Med. 17:320–29.
  • Borgfeldt C, Hansson SR, Gustavsson B, Måsbäck A, Casslén B. 2001. Dedifferentiation of serous ovarian cancer from cystic to solid tumors is associated with increased expression of mRNA for urokinase plasminogen activator (uPA), its receptor (uPAR) and its inhibitor (PAI-1). Int J Cancer 15. 92(4):497–502.
  • Bougherara H, Mansuet-Lupo A, Alifano M, Ngô C, Damotte D, Le Frère-Belda MA, Donnadieu E, Peranzoni E. 2015. Real-time imaging of resident T cells in human lung and ovarian carcinomas reveals how different tumor microenvironments control T lymphocyte migration. Front Immunol. 12;6:500.
  • Bougie O, Weberpals JI. 2011. Clinical considerations of BRCA1- and BRCA2-mutation carriers: a review. Int J Surg Oncol. 2011:374012.
  • Boyd RS, Balkwill FR. 1999. MMP-2 release and activation in ovarian carcinoma: the role of fibroblasts. Br J Cancer. 80(3–4):315–21.
  • Bremnes RM, Dønnem T, Al-Saad S, Al-Shibli K, Andersen S, Sirera R, Camps C, Marinez I, Busund LT. 2011. The role of tumor stroma in cancer progression and prognosis: emphasis on carcinoma-associated fibroblasts and non-small cell lung cancer. J Thorac Oncol. 6:209–17.
  • Bruchard M, Mignot G, Derangère V. 2013. Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth. Nat Med. 19:57–64.
  • Buache É, Rio MC. 2014. The tumoral stroma, a breeding ground for cancer cells. Med Sci (Paris). 30(4):385–90.
  • Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H. 2011. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 365:2473–83.
  • Chaffer CL, Weinberg RA. 2011. A perspective on cancer cell metastasis. Science. 331:1559–64.
  • Chang HY, Chi JT, Dudoit S, Bondre C, van de Rijn M, Botstein D, Brown PO. 2002. Diversity, topographic differentiation, and positional memory in humanfibroblasts. Proc Natl Acad Sci U S A. 99:12877–82.
  • Cherng S, Young J, Ma H. 2008. Alpha-smooth muscle actin (α-SMA). J Am Sci. 4:10.
  • Cirri P, Chiarugi P. 2011. Cancer associated fibroblasts: the dark side of the coin. Am J Cancer Res. 1:482–97.
  • Cohen SJ, Alpaugh RK, Palazzo I, Meropol NJ, Rogatko A, Xu Z, Hoffman JP, Weiner LM, Cheng JD. 2008. Fibroblast activation protein and its relationship to clinical outcome in pancreatic adenocarcinoma. Pancreas. 37:154–58.
  • Colvin EK. 2014. Tumor-associated macrophages contribute to tumor progression in ovarian cancer. Front Oncol. 4:137.
  • Coussens LM, Werb Z. 2002. Inflammation and cancer. Nature. 420:860–67.
  • Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, et al. 2004. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 10(9):942–49.
  • Da Silva AC, Jammal MP, Etchebehere RM, Murta EFC, Nomelini RS. 2018. Role of alpha-smooth muscle actin and fibroblast activation protein alpha in ovarian neoplasms. Gynecol Obstet Invest. 83:381–87.
  • Davidson B, Trope CG, Reich R. 2014. The role of the tumor stroma in ovarian cancer. Front Oncol. 4:104.
  • De Wever O, Mareel M. 2003. Role of tissue stroma in cancer cell invasion. J Pathol. 200:429–47.
  • Dirkx AE, Oude Egbrink MG, Wagstaff J, Griffioen AW. 2006. Monocyte/macrophage infiltration in tumors: modulators of angiogenesis. J Leukoc Biol. 80:1183–96.
  • Donnem T, Al-Shibli K, Al-Saad S, Busund LT, Bremnes RM. 2009. Prognostic impact of fibroblast growth factor 2 in non-small cell lung cancer: coexpression withVEGFR-3 and PDGF-B predicts poor survival. J Thorac Oncol. 4:578–85.
  • Dvorak HF, Senger DR, Dvorak AM. 1983. Fibrin as a component of the tumor stroma: origins and biological significance. Cancer Metastasis Rev. 2:41–73.
  • Egeblad M, Rasch MG, Weaver VM. 2010. Dynamic interplay between the collagen scaffold and tumor evolution. Curr Opin Cell Biol. 22:697–706.
  • Eo WK, Kim KH, Park EJ, Kim HY, Kim HB, Koh SB, Namkung J. 2018. Diagnostic accuracy of inflammatory markers for distinguishing malignant and benign ovarian masses. J Cancer. 9:1165–72.
  • Erez N, Glanz S, Raz Y, Avivi C, Barshack I. 2013. Cancer associated fibroblasts express pro-inflammatory factors in human breast and ovarian tumors. Biochem Biophys Res Commun. 2; 437(3):397–402.
  • Ferrara N. 2005. VEGF as a therapeutic target in cancer. Oncology. 69(Suppl3):11–16.
  • Folkman J. 1971. Tumor angiogenesis: therapeutic implications. N Engl J Med. 285:1182–86.
  • Folkman J. 1972. Anti-angiogenesis: new concept for therapy of solid tumors. Ann Surg. 175:409–16.
  • Foster DS, Jones RE, Ransom RC, Longaker MT, Norton JA. 2018. The evolving relationship of wound healing and tumor stroma. JCI Insight. 20;3(18). doi:10.1016/0006-2952(75)90415-3
  • Franco OE, Shaw AK, Strand DW, Hayward SW. 2010. Cancer associated fibroblasts in cancer pathogenesis. Semin Cell Dev Biol. 21:33–39.
  • Freedman RS, Deavers M, Liu J, Wang E. 2004. Peritoneal inflammation - A microenvironment for epithelial ovarian cancer (EOC). J Transl Med. 2:23.
  • Fridman WH, Sautès-Fridman C. 2014. Le microenvironnement tumoral: matrice nourricière, champ de bataille etcible thérapeutique des cancers. Med Sci (Paris). 30:359–65.
  • Gerhardt H, Betsholtz C. 2003. Endothelial-pericyte interactions in angiogenesis. Cell Tissue Res. 314:15–23.
  • Goff BA, Mandel LS, Melancon CH, Muntz HG. 2004. Frequency of symptoms of ovarian cancer in women presenting to primary care clinics. JAMA. 291:2705–12.
  • Gualandris A, Rusnati M, Belleri M, Nelli EE, Bastaki M, Molinari-Tosatti MP, Bonardi F, Parolini S, Albini A, Morbidelli L, et al. 1996. Basic fibroblast growth factor overexpression in endothelial cells: an autocrine mechanism for angiogenesis and angioproliferative diseases. Cell Growth Differ. 7:147–60.
  • Hanahan D, Folkman J. 1996. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 9;86(3):353–64.
  • Hanahan D, Weinberg RA. 2000. The hallmarks of cancer. Cell. 100:57–70.
  • Hansen JM, Coleman RL, Sood AK. 2016. Targeting the tumour microenvironment in ovarian cancer. Eur J Cancer. 56:131–43.
  • Hashimoto Y, Skacel M, Adams JC. 2005. Roles of fascin in human carcinoma motility and signaling: prospects for a novel biomarker? Int J Biochem Cell Biol. 37:1787–804.
  • Haviv I, Polyak K, Qiu W, Hu M, Campbell I. 2009. Origin of carcinoma associated fibroblasts. Cell Cycle. 8:589–95.
  • Henry LR, Lee HO, Lee JS, Klein-Szanto A, Watts P, Ross EA, Chen WT, Cheng JD. 2007. Clinical implications of fibroblast activation protein in patients with colon cancer. Clin Cancer Res. 13:1736–41.
  • Holmgren L, O’Reilly MS, Folkman J. 1995. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med. 1:149–53.
  • Hughes CC. 2008. Endothelial-stromal interactions in angiogenesis. Curr Opin Hematol. 15:204–09.
  • Jammal MP, Martins-Filho A, Silveira TP, Murta EF, Nomelini RS. 2016. Cytokines and prognostic factors in epithelial ovarian cancer. Clin Med Insights Oncol. 10:71–76.
  • Jawhari AU, Buda A, Jenkins M, Shehzad K, Sarraf C, Noda M, Farthing MJ, Pignatelli M, Adams JC. 2003. Fascin, an actin-bundling protein, modulates colonic epithelial cell invasiveness and differentiation in vitro. Am J Pathol. 162:69–80.
  • Joyce JA, Fearon DT. 2015. T cell exclusion, immune privilege, and the tumor microenvironment. Science. 348:74–80.
  • Kalluri R, Weinberg RA. 2009. The basics of epithelial-mesenchymal transition. J Clin Invest. 119:1420–28.
  • Kalluri R, Zeisberg M. 2006. Fibroblasts in cancer. Nat Rev Cancer. 6:392–401.
  • Kelly T, Huang Y, Simms AE, Mazur A. 2012. Fibroblast activation protein-α: a key modulator of the microenvironment in multiple pathologies. Int Rev Cell Mol Biol. 297:83–116.
  • Kelly-Goss MR, Sweat RS, Stapor PC, Peirce SM, Murfee WL. 2014. Targeting pericytes for angiogenic therapies. Microcirculation. 21:345–57.
  • Kenny HA, Krausz T, Yamada SD, Lengyel E. 2007. Use of a novel 3d culture model to elucidate the role of mesothelial cells, fibroblasts and extra-cellular matrices on adhesion and invasion of ovarian cancer cells to the omentum. Int J Cancer. 121:1463–72.
  • Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS, Ferrara N. 1993. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature. 362:841–44.
  • Klotzsch E, Smith ML, Kubow KE, Muntwyler S, Little WC, Beyeler F, Gourdon D, Nelson BJ, Vogel V. 2009. Fibronectin forms the most extensible biological fibers displaying switchable force-exposed cryptic binding sites. Proc Natl Acad Sci USA. 106(43):18267–72.
  • Klymenko Y, Kim O, Loughran E, Yang J, Lombard R, Alber M, Stack MS. 2017. Cadherin composition and multicellular aggregate invasion in organotypic models of epithelial ovarian cancer intraperitoneal metastasis. Oncogene. 36:5840–51.
  • Labiche A, Heutte N, Herlin P, Chasle J, Gauduchon P, Elie N. 2010. Stromal compartment as a survival prognostic factor in advanced ovarian carcinoma. Int J Gynecol Cancer. 20:28–33.
  • Lai D, Ma L, Wang F. 2012. Fibroblast activation protein regulates tumor-associated fibroblasts and epithelial ovarian cancer cells. Int J Oncol. 41:541–50.
  • Lau TS, Chan LK, Wong EC, Hui CW, Sneddon K, Cheung TH, Yim SF, Lee JH, Yeung CS, Chung TK, et al. 2017. A loop of cancer-stroma-cancer interaction promotes peritoneal metastasis of ovarian cancer via TNFα-TGFα-EGFR. Oncogene. 36:3576–87.
  • Leffers N, Gooden MJ, de Jong RA, Hoogeboom BN, Ten Hoor KA, Hollema H, Boezen HM, van der Zee AG, Daemen T, Nijman HW. 2009. Prognostic significance of tumor-infiltrating T-lymphocytes in primary and metastatic lesions of advanced stage ovarian cancer. Cancer Immunol Immunother. 58(3):449–59.
  • Lengyel E. 2010. Ovarian cancer development and metastasis. Am J Pathol. 177:1053–64.
  • Levental KR, Yu H, Kass L, Lakins JN, Egeblad M, Erler JT, Fong SF, Csiszar K, Giaccia A, Weninger W, et al. 2009. Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell. 139:891–906.
  • Li J, Wang J, Chen R, Bai Y, Lu X. 2017. The prognostic value of tumor-infiltrating T lymphocytes in ovarian cancer. Oncotarget. 8:15621–31.
  • Li J, Wei Y, Liu K, Yuan C, Tang Y, Quan Q, Chen P, Wang W, Hu H, Yang L. 2010. Synergistic effects of FGF-2 and PDGF-BB on angiogenesis and muscle regeneration in rabbit hindlimb ischemia model. Microvasc Res. 80:10–17.
  • Li J, Zhang S, Pei M, Wu L, Liu Y, Li H, Lu J, Li X. 2018. Promotes epithelial-mesenchymal transition through increasing snail1 in ovarian cancer cells. Cell Physiol Biochem. 49:1766–77.
  • Li J, Zhou BP. 2011. Activation of β-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters. BMC Cancer. 11:49.
  • Linares PM, Chaparro M, Gisbert JP. 2014. Angiopoietins in inflammation and their implication in the development of inflammatory bowel disease. A Review J Crohns Colitis. 8:183–90.
  • Loughran EA, Leonard AK, Hilliard TS, Phan RC, Yemc MG, Harper E, Sheedy E, Klymenko Y, Asem M, Liu Y, et al. 2018. Aging increases susceptibility to ovarian cancer metastasis in murine allograft models and alters immune composition of peritoneal adipose tissue. Neoplasia. 20:621–31.
  • Lu P, Weaver VM, Werb Z. 2012. The extracellular matrix: a dynamic niche in cancer progression. J Cell Biol. 196:395–406.
  • Mabuchi S, Terai Y, Morishige K, Tanabe-Kimura A, Sasaki H, Kanemura M, Tsunetoh S, Tanaka Y, Sakata M, Burger RA, et al. 2008. Maintenance treatment with bevacizumab prolongs survival in an in vivo ovarian cancer model. Clin Cancer Res. 1;14(23):7781–89.
  • Mantovani A, Allavena P, Sica A, Balkwill F. 2008. Cancer-related inflammation. Nature. 454:436–44.
  • Mao Y, Keller ET, Garfield DH, Shen K, Wang J. 2013. Stromal cells in tumor microenvironment and breast cancer. Cancer Metastasis Rev. 32:303–15.
  • Marastoni S, Ligresti G, Lorenzon E, Colombatti A, Mongiat M. 2008. Extracellular matrix: a matter of life and death. Connect Tissue Res. 49:203–06.
  • Matte I, Lane D, Laplante C, Rancourt C, Piché A. 2012. Profiling of cytokines in human epithelial ovarian cancer ascites. Am J Cancer Res. 2:566–80.
  • McHugh KM, Crawford K, Lessard JL. 1991. A comprehensive analysis of the developmental and tissue-specific expression of the isoactin multigene family in the rat. Dev Biol. 148:442–58.
  • McPherson K, Steel CM, Dixon JM. 2000. ABC of breast diseases. Breast cancer-epidemiology, risk factors, and genetics. BMJ. 321(7261):624–28.
  • Medina L, Rabinovich A, Piura B, Dyomin V, Levy RS, Huleihel M. 2014. Expression of IL-18, IL-18 binding protein, and IL-18 receptor by normal and cancerous human ovarian tissues: possible implication of IL-18 in the pathogenesis of ovarian carcinoma. Mediators Inflamm. 2014:914954.
  • Mhawech-Fauceglia P, Yan L, Sharifian M, Ren X, Liu S, Kim G, Gayther SA, Pejovic T, Lawrenson K. 2015. Stromal expression of fibroblast activation protein alpha (FAP) predicts platinum resistance and shorter recurrence in patients with epithelial ovarian cancer. Cancer Microenviron. 8:23–31.
  • Miron RJ, Fujioka-Kobayashi M, Bishara M, Zhang Y, Hernandez M, Choukroun J. 2017. Platelet-rich fibrin and soft tissue wound healing: a systematic review. Tissue Eng Part B Rev. 23:83–99.
  • Miwa T, Manabe Y, Kurokawa K, Kamada S, Kanda N, Bruns G, Ueyama H, Kakunaga T. 1991. Structure, chromosome location, and expression of the human smooth muscle (enteric type) gamma-actin gene: evolution of six human actin genes. Mol Cell Biol. 11:3296–306.
  • Mohan RR, Gupta R, Mehan MK, Cowden JW, Sinha S. 2010. Decorin transfection suppresses profibrogenic genes and myofibroblast formation in human corneal fibroblasts. Exp Eye Res. 91:238–45.
  • Monk BJ, Minion LE, Coleman RL. 2016. Anti-angiogenic agents in ovarian cancer: past, present, and future. Ann Oncol. 27:i33–i39.
  • Munn LL. 2017. Cancer and inflammation. Wiley Interdiscip Rev Syst Biol Med. 9:2.
  • Muñoz-Chápuli R, Quesada AR, Angel Medina M. 2004. Angiogenesis and signaltransduction in endothelial cells. Cell Mol Life Sci. 61:2224–43.
  • Nezhat F, Datta MS, Hanson V, Pejovic T, Nezhat C, Nezhat C. 2008. The relationship of endometriosis and ovarian malignancy: a review. Fertil Steril. 90:1559–70.
  • Noy R, Pollard JW. 2014. Tumor-associated macrophages: from mechanisms to therapy. Immunity. 41:49–61.
  • Ohkura N, Kitagawa Y, Sakaguchi S. 2013. Development and maintenance of regulatory T cells. Immunity. 38:414–23.
  • Ostman A, Heldin CH. 2007. PDGF receptors as targets in tumor treatment. Adv Cancer Res. 97:247–74.
  • Ozbek S, Balasubramanian PG, Chiquet-Ehrismann R, Tucker RP, Adams JC. 2010. The evolution of extracellular matrix. Mol Biol Cell. 21:4300–05.
  • Paszek MJ, Zahir N, Johnson KR, Lakins JN, Rozenberg GI, Gefen A, Reinhart-King CA, Margulies SS, Dembo M, Boettiger D, et al. 2005. Tensional homeostasis and the malignant phenotype. Cancer Cell. 8:241–54.
  • Polgár L. 2002. The prolyl oligopeptidase family. Cell Mol Life Sci. 59:349–62.
  • Pollard JW. 2004. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer. 4:71–78.
  • Pollard JW. 2009. Trophic macrophages in development and disease. Nat Rev Immunol. 9:259–70.
  • Radisky ES, Radisky DC. 2010. Matrix metalloproteinase-induced epithelial-mesenchymal transition in breast cancer. J Mammary Gland Biol Neoplasia. 15:201–12.
  • Raza A, Franklin MJ, Dudek AZ. 2010. Pericytes and vessel maturation during tumor angiogenesis and metastasis. Am J Hematol. 85:593–98.
  • Risau W, Flamme I. 1995. Vasculogenesis. Annu Rev Cell Dev Biol. 11:73–91.
  • Rønnov-Jessen L, Petersen OW, Bissell MJ. 1996. Cellular changes involved in conversion of normal to malignant breast: importance of the stromal reaction. Physiol Rev. 76:69–125.
  • Roviello G, Bachelot T, Hudis CA. 2017. The role of bevacizumab in solid tumours: A literature based meta-analysis of randomised trials. Eur J Cancer. 75:245–58.
  • Ruan G, Ye L, Liu G, An J, Sehouli J, Sun P. 2018. The role of bevacizumab in targeted vascular endothelial growth factor therapy for epithelial ovarian cancer: an updated systematic review and meta-analysis. Onco Targets Ther. 11:521–28.
  • Ryner L, Guan Y, Firestein R, Xiao Y, Choi Y, Rabe C, Lu S, Fuentes E, Huw LY, Lackner MR, et al. 2015. Upregulation of periostin and reactive stroma is associated with primary chemoresistance and predicts clinical outcomes in epithelial ovarian cancer. Clin Cancer Res. 21:2941–51.
  • Saad AF, Hu W, Sood AK. 2010. Microenvironment and pathogenesis of epithelial ovarian cancer. Horm Cancer. 1:277–90.
  • Santra M, Skorski T, Calabretta B, Lattime EC, Iozzo RV. 1995. De novo decorin gene expression suppresses the malignant phenotype in human colon cancer cells. Proc Natl Acad Sci USA. 92:7016–20.
  • Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C, et al. 2005. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci U S A. 20;102(51):18538–43.
  • Scanlan MJ, Raj BK, Calvo B, Garin-Chesa P, Sanz-Moncasi MP, Healey JH, Old LJ, Rettig WJ. 1994. Molecular cloning of fibroblast activation protein alpha, a member of the serine protease family selectively expressed in stromal fibroblasts of epithelial cancers. Proc Natl Acad Sci USA. 91:5657–61.
  • Schnittert J, Bansal R, Storm G, Prakash J. 2018. Integrins in wound healing, fibrosis and tumor stroma: high potential targets for therapeutics and drug delivery. Adv Drug Deliv Rev. 129:37–53.
  • Schreiber RD, Old LJ, Smyth MJ. 2011. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 331:1565–70.
  • Seynhaeve ALB, Oostinga D, van Haperen R, Eilken HM, Adams S, Adams RH, TenHagen TLM. 2018. Spatiotemporal endothelial cell - pericyte association in tumors as shown by high resolution 4D intravital imaging. Sci Rep. 8:9596.
  • Shang Y, Cai X, Fan D. 2013. Roles of epithelial-mesenchymal transition in cancer drug resistance. Curr Cancer Drug Targets. 13:915–29.
  • Shepro D, Morel NM. 1993. Pericyte physiology. Faseb J. 7:1031–38.
  • Shi M, Yu DH, Chen Y, Zhao CY, Zhang J, Liu QH, Ni CR, Zhu MH. 2012. Expression of fibroblast activation protein in human pancreatic adenocarcinoma and its clinicopathological significance. World J Gastroenterol. 18:840–46.
  • Shiga K, Hara M, Nagasaki T, Sato T, Takahashi H, Takeyama H. 2015. Cancer-associated fibroblasts: their characteristics and their roles in tumor growth. Cancers (Basel). 7:2443–58.
  • Shih I, Kurman RJ. 2004. Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. Am J Pathol. 164:1511–18.
  • Shinde AV, Humeres C, Frangogiannis NG. 2016. The role of alpha-smooth muscle actin in fibroblast-mediated matrix contraction and remodeling. Biochim Biophys Acta. 1863:298–309.
  • Sica A, Saccani A, Mantovani A. 2002. Tumor-associated macrophages: a molecular perspective. Int Immunopharmacol. 2:1045–54.
  • Sica A, Schioppa T, Mantovani A, Allavena P. 2006. Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer. 42:717–27.
  • Skalli O, Ropraz P, Trzeciak A, Benzonana G, Gillessen D, Gabbiani G. 1986. A monoclonal antibody against alpha-smooth muscle actin: a new probe for smooth muscle differentiation. J Cell Biol. 103:2787–96.
  • Solinas G, Germano G, Mantovani A, Allavena P. 2009. Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J Leukoc Biol. 86:1065–73.
  • Spaeth EL, Dembinski JL, Sasser AK, Watson K, Klopp A, Hall B, Andreeff M, Marini F. 2009. Mesenchymal stem cell transition to tumor-associated fibroblasts contributes to fibrovascular network expansion and tumor progression. PLoS One. 4:e4992.
  • Spaw M, Anant S, Thomas SM. 2017. Stromal contributions to the carcinogenic process. Mol Carcinog. 56:1199–213.
  • Stapor PC, Sweat RS, Dashti DC, Betancourt AM, Murfee WL. 2014. Pericyte dynamics during angiogenesis: new insights from new identities. J Vasc Res. 51:163–74.
  • Sun KH, Chang Y, Reed NI, Sheppard D. 2016. α-Smooth muscle actin is an inconsistent marker of fibroblasts responsible for force-dependent TGFβ activation or collagen production across multiple models of organ fibrosis. Am J Physiol Lung Cell Mol Physiol. 310:L824–36.
  • Tan H, He Q, Gong G, Wang Y, Li J, Wang J, Zhu D, Wu X. 2016. miR-382 inhibits migration and invasion by targeting ROR1 through regulating EMT in ovarian cancer. Int J Oncol. 48:181–90.
  • Theocharis AD, Skandalis SS, Gialeli C, Karamanos NK. 2016. Extracellular matrix structure. Adv Drug Deliv Rev. 97:4–27.
  • Thiery JP. 2002. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2:442–54.
  • Toker A, Nguyen LT, Stone SC, Yang SYC, Katz SR, Shaw PA, Clarke BA, Ghazarian D, Al-Habeeb A, Easson A, et al. 2018. Regulatory T cells in ovarian cancer are characterized by a highly activated phenotype distinct from that in melanoma. Clin Cancer Res. 15;24(22):5685–96.
  • Tomsová M, Melichar B, Sedláková I, Steiner I. 2008. Prognostic significance of CD3+ tumor infiltrating lymphocytes in ovarian carcinoma. Gynecol Oncol. 108:415–20.
  • Tracy LE, Minasian RA, Caterson EJ. 2016. Extracellular matrix and dermal fibroblast function in the healing wound. Adv Wound Care (New Rochelle). 5:119–36.
  • Vandekerckhove J, Weber K. 1978. At least six different actins are expressed in a higher mammal: an analysis based on the amino acid sequence of the amino-terminal tryptic peptide. J Mol Biol. 126:783–802.
  • Wang E, Ngalame Y, Panelli MC, Nguyen-Jackson H, Deavers M, Mueller P, Hu W, Savary CA, Kobayashi R, Freedman RS, et al. 2005. Peritoneal and subperitoneal stroma may facilitate regional spread of ovarian cancer. Clin Cancer Res. 11:113–22.
  • Weymouth N, Shi Z, Rockey DC. 2012. Smooth muscle α actin is specifically required for the maintenance of lactation. Dev Biol. 363:1–14.
  • Xu M, Cao FL, Li N, Gao X, Su X, Jiang X. 2018. Leptin induces epithelial-to-mesenchymal transition via activation of the ERK signaling pathway in lung cancer cells. Oncol Lett. 16:4782–88.
  • Yamaguchi Y, Mann DM, Ruoslahti E. 1990. Negative regulation of transforming growth factor-beta by the proteoglycan decorin. Nature. 346:281–84.
  • Yilmaz M, Christofori G, Lehembre F. 2007. Distinct mechanisms of tumor invasion and metastasis. Trends Mol Med. 13:535–41.
  • Ying X, Wei K, Lin Z, Cui Y, Ding J, Chen Y, Xu B. 2016. MicroRNA-125b suppresses ovarian cancer progression via suppression of the epithelial-mesenchymal transition pathway by targeting the SET protein. Cell Physiol Biochem. 39:501–10.
  • Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN, et al. 2003. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 16;348(3):203–13.
  • Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Zhang M, He Y, Sun X, Li Q, et al. 2014. A high M1/M2 ratio of tumor-associated macrophages is associated with extended survival in ovarian cancer patients. J Ovarian Res. 7:19.
  • Zhang Y, Tang H, Cai J, Zhang T, Guo J, Feng D, Wang Z. 2011. Ovarian cancer-associated fibroblasts contribute to epithelial ovarian carcinoma metastasis by promoting angiogenesis, lymphangiogenesis and tumor cell invasion. Cancer Lett. 303:47–55.

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