Embryonic stem cell secreted factors decrease invasiveness of triple-negative breast cancer cells through regulome modulation

References

• American Cancer Society. Cancer facts & figures. Atlanta: American Cancer Society; 2015.
   Google Scholar
• Soltanian S, Matin MM. Cancer stem cells and cancer therapy. Tumour Biol. 2011;32(3):425–440. doi:10.1007/s13277-011-0155-8.
   PubMed Web of Science ®Google Scholar
• Huang Y, Anderle P, Bussey KJ, Barbacioru C, Shankavaram U, Dai Z, Reinhold WC, Papp A, Weinstein JN, Sadee W. Membrane transporters and channels: Role of the transportome in cancer chemosensitivity and chemoresistance. Cancer Res. 2004;64(12):4294–4301. doi:10.1158/0008-5472.CAN-03-3884.
   PubMed Web of Science ®Google Scholar
• Fillmore CM, Kuperwasser C. Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy. Breast Cancer Res. 2008. 10(2):R25. doi:10.1186/bcr1982.
   PubMed Web of Science ®Google Scholar
• Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, et al. Aldh1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007;1(5):555–567. doi:10.1016/j.stem.2007.08.014.
   PubMed Web of Science ®Google Scholar
• Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, Pilotti S, Pierotti MA, Daidone MG. Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res. 2005;65(13):5506–5511. doi:10.1158/0008-5472.CAN-05-0626.
   PubMed Web of Science ®Google Scholar
• Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer. 2005. 5(4):275–284. doi:10.1038/nrc1590.
   PubMed Web of Science ®Google Scholar
• Gil J, Stembalska A, Pesz KA, Sasiadek MM. Cancer stem cells: The theory and perspectives in cancer therapy. J Appl Genet. 2008;49(2):193–199. doi:10.1007/BF03195612.
   PubMed Web of Science ®Google Scholar
• Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003;100(7):3983–3988. doi:10.1073/pnas.0530291100.
   PubMed Web of Science ®Google Scholar
• Shimono Y, Zabala M, Cho RW, Lobo N, Dalerba P, Qian D, Diehn M, Liu H, Panula SP, Chiao E, et al. Downregulation of mirna-200c links breast cancer stem cells with normal stem cells. Cell. 2009;138(3):592–603. doi:10.1016/j.cell.2009.07.011.
   PubMed Web of Science ®Google Scholar
• Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell. 2011;144(5):646–674. doi:10.1016/j.cell.2011.02.013.
   PubMed Web of Science ®Google Scholar
• Yaacoub K, Pedeux R, Tarte K, Guillaudeux T. Role of the tumor microenvironment in regulating apoptosis and cancer progression. Cancer Lett. 2016;378(2):150–9. doi:10.1016/j.canlet.2016.05.012.
   PubMed Web of Science ®Google Scholar
• Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105–111. doi:10.1038/35102167.
   PubMed Web of Science ®Google Scholar
• Kim J, Orkin SH. Embryonic stem cell-specific signatures in cancer: Insights into genomic regulatory networks and implications for medicine. Genome Med. 2011;3(11):75. doi:10.1186/gm291.
   PubMedGoogle Scholar
• Abbott DE, Bailey CM, Postovit LM, Seftor EA, Margaryan N, Seftor RE, Hendrix MJ. The epigenetic influence of tumor and embryonic microenvironments: How different are they? Cancer Microenviron. 2008;1(1):13–21. doi:10.1007/s12307-008-0004-5.
   PubMedGoogle Scholar
• Graf T, Enver T. Forcing cells to change lineages. Nature. 2009;462(7273):587–594. doi:10.1038/nature08533.
   PubMed Web of Science ®Google Scholar
• Rajapakse I, Groudine M, Mesbahi M. Dynamics and control of state-dependent networks for probing genomic organization. Proc Natl Acad Sci U S A. 2011;108(42):17257–17262. doi:10.1073/pnas.1113249108.
   PubMed Web of Science ®Google Scholar
• Xu C, Inokuma MS, Denham J, Golds K, Kundu P, Gold JD, Carpenter MK. Feeder-free growth of undifferentiated human embryonic stem cells. Nat Biotech. 2001;19(10):971–974. doi:10.1038/nbt1001-971.
   PubMed Web of Science ®Google Scholar
• Ayuzawa R, Doi C, Rachakatla RS, Pyle MM, Maurya DK, Troyer D, Tamura M. Naive human umbilical cord matrix derived stem cells significantly attenuate growth of human breast cancer cells in vitro and in vivo. Cancer Lett. 2009;280(1):31–37. doi:10.1016/j.canlet.2009.02.011.
   PubMed Web of Science ®Google Scholar
• Giuffrida D, Rogers IM, Nagy A, Calogero AE, Brown TJ, Casper RF. Human embryonic stem cells secrete soluble factors that inhibit cancer cell growth. Cell Prolif. 2009;42(6):788–798. doi:10.1111/j.1365-2184.2009.00640.x.
   PubMed Web of Science ®Google Scholar
• Kulesa PM, Kasemeier-Kulesa JC, Teddy JM, Margaryan NV, Seftor EA, Seftor RE, Hendrix MJ. Reprogramming metastatic melanoma cells to assume a neural crest cell-like phenotype in an embryonic microenvironment. Proc Natl Acad Sci U S A. 2006;103(10):3752–3757. doi:10.1073/pnas.0506977103.
   PubMed Web of Science ®Google Scholar
• Postovit LM, Seftor EA, Seftor RE, Hendrix MJ. A three-dimensional model to study the epigenetic effects induced by the microenvironment of human embryonic stem cells. Stem Cells. 2006;24(3):501–505. doi:10.1634/stemcells.2005-0459.
   PubMed Web of Science ®Google Scholar
• Postovit LM, Margaryan NV, Seftor EA, Kirschmann DA, Lipavsky A, Wheaton WW, Abbott DE, Seftor RE, Hendrix MJ. Human embryonic stem cell microenvironment suppresses the tumorigenic phenotype of aggressive cancer cells. Proc Natl Acad Sci U S A. 2008;105(11):4329–4334. doi:10.1073/pnas.0800467105.
   PubMed Web of Science ®Google Scholar
• Qiao L, Xu Z, Zhao T, Zhao Z, Shi M, Zhao RC, Ye L, Zhang X. Suppression of tumorigenesis by human mesenchymal stem cells in a hepatoma model. Cell Res. 2008;18(4):500–507. doi:10.1038/cr.2008.40.
   PubMed Web of Science ®Google Scholar
• Sun B, Yu KR, Bhandari DR, Jung JW, Kang SK, Kang KS. Human umbilical cord blood mesenchymal stem cell-derived extracellular matrix prohibits metastatic cancer cell mda-mb-231 proliferation. Cancer Lett. 2010;296(2):178–185. doi:10.1016/j.canlet.2010.04.007.
   PubMed Web of Science ®Google Scholar
• Qiao L, Xu ZL, Zhao TJ, Ye LH, Zhang XD. Dkk-1 secreted by mesenchymal stem cells inhibits growth of breast cancer cells via depression of wnt signalling. Cancer Lett. 2008;269(1):67–77. doi:10.1016/j.canlet.2008.04.032.
   PubMed Web of Science ®Google Scholar
• Bellis AD, Penalver-Bernabe B, Weiss MS, Yarrington ME, Barbolina MV, Pannier AK, Jeruss JS, Broadbelt LJ, Shea LD. Cellular arrays for large-scale analysis of transcription factor activity. Biotechnol Bioeng. 2011;108(2):395–403. doi:10.1002/bit.22916.
   PubMed Web of Science ®Google Scholar
• Siletz A, Schnabel M, Kniazeva E, Schumacher AJ, Shin S, Jeruss JS, Shea LD. Dynamic transcription factor networks in epithelial-mesenchymal transition in breast cancer models. PLoS One. 2013;8(4):e57180. doi:10.1371/journal.pone.0057180.
   PubMed Web of Science ®Google Scholar
• Weiss MS, Penalver Bernabe B, Bellis AD, Broadbelt LJ, Jeruss JS, Shea LD. Dynamic, large-scale profiling of transcription factor activity from live cells in 3d culture. PLoS One. 2010;5(11):e14026. doi:10.1371/journal.pone.0014026.
   PubMed Web of Science ®Google Scholar
• Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139(5):871–890. doi:10.1016/j.cell.2009.11.007.
   PubMed Web of Science ®Google Scholar
• Vierbuchen T, Wernig M. Direct lineage conversions: Unnatural but useful? Nat Biotechnol. 2011;29(10):892–907. doi:10.1038/nbt.1946.
   PubMed Web of Science ®Google Scholar
• Ginis I, Luo Y, Miura T, Thies S, Brandenberger R, Gerecht-Nir S, Amit M, Hoke A, Carpenter MK, Itskovitz-Eldor J, et al. Differences between human and mouse embryonic stem cells. Dev Biol. 2004;269(2):360–380. doi:10.1016/j.ydbio.2003.12.034.
   PubMed Web of Science ®Google Scholar
• Lin S, Lin Y, Nery JR, Urich MA, Breschi A, Davis CA, Dobin A, Zaleski C, Beer MA, Chapman WC, et al. Comparison of the transcriptional landscapes between human and mouse tissues. Proc Natl Acad Sci U S A. 2014;111(48):17224–17229. doi:10.1073/pnas.1413624111.
   PubMed Web of Science ®Google Scholar
• Sheridan C, Kishimoto H, Fuchs RK, Mehrotra S, Bhat-Nakshatri P, Turner CH, Goulet R, Jr., Badve S, Nakshatri H. Cd44+/cd24- breast cancer cells exhibit enhanced invasive properties: An early step necessary for metastasis. Breast Cancer Res. 2006;8(5):R59. doi:10.1186/bcr1610.
   PubMed Web of Science ®Google Scholar
• Scheel C, Weinberg RA. Cancer stem cells and epithelial-mesenchymal transition: Concepts and molecular links. Semin Cancer Biol. 2012;22(5-6):396–403. doi:10.1016/j.semcancer.2012.04.001.
   PubMed Web of Science ®Google Scholar
• Chu IM, Lai WC, Aprelikova O, El Touny LH, Kouros-Mehr H, Green JE. Expression of gata3 in mda-mb-231 triple-negative breast cancer cells induces a growth inhibitory response to tgfss. PLoS One. 2013;8(4):e61125. doi:10.1371/journal.pone.0061125.
   PubMed Web of Science ®Google Scholar
• Mehra R, Varambally S, Ding L, Shen R, Sabel MS, Ghosh D, Chinnaiyan AM, Kleer CG. Identification of gata3 as a breast cancer prognostic marker by global gene expression meta-analysis. Cancer Res. 2005;65(24):11259–11264.
   Google Scholar
• Topczewska JM, Postovit LM, Margaryan NV, Sam A, Hess AR, Wheaton WW, Nickoloff BJ, Topczewski J, Hendrix MJ. Embryonic and tumorigenic pathways converge via nodal signaling: Role in melanoma aggressiveness. Nat Med. 2006;12(8):925–932. doi:10.1038/nm1448.
   PubMed Web of Science ®Google Scholar
• Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013;19(11):1423–1437. doi:10.1038/nm.3394.
   PubMed Web of Science ®Google Scholar
• Charafe-Jauffret E, Ginestier C, Iovino F, Wicinski J, Cervera N, Finetti P, Hur MH, Diebel ME, Monville F, Dutcher J, et al. Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature. Cancer Res. 2009;69(4):1302–1313. doi:10.1158/0008-5472.CAN-08-2741.
   PubMed Web of Science ®Google Scholar
• Borgna S, Armellin M, di Gennaro A, Maestro R, Santarosa M. Mesenchymal traits are selected along with stem features in breast cancer cells grown as mammospheres. Cell Cycle. 2012;11(22):4242–4251. doi:10.4161/cc.22543.
   PubMed Web of Science ®Google Scholar
• Thakur R, Trivedi R, Rastogi N, Singh M, Mishra DP. Inhibition of stat3, fak and src mediated signaling reduces cancer stem cell load, tumorigenic potential and metastasis in breast cancer. Sci Rep. 2015;5:10194. doi:10.1038/srep10194.
   PubMed Web of Science ®Google Scholar
• Bissell MJ, Radisky D. Putting tumours in context. Nat Rev Cancer. 2001;1(1):46–54. doi:10.1038/35094059.
   PubMed Web of Science ®Google Scholar
• Li L, Neaves WB. Normal stem cells and cancer stem cells: The niche matters. Cancer Res. 2006;66(9):4553–4557. doi:10.1158/0008-5472.CAN-05-3986.
   PubMed Web of Science ®Google Scholar
• Huber MA, Azoitei N, Baumann B, Grunert S, Sommer A, Pehamberger H, Kraut N, Beug H, Wirth T. Nf-kappab is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression. J Clin Invest. 2004;114(4):569–581. doi:10.1172/JCI200421358.
   PubMed Web of Science ®Google Scholar
• Wong CC, Gilkes DM, Zhang H, Chen J, Wei H, Chaturvedi P, Fraley SI, Wong CM, Khoo US, Ng IO, et al. Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation. Proc Natl Acad Sci U S A. 2011;108(39):16369–16374. doi:10.1073/pnas.1113483108.
   PubMed Web of Science ®Google Scholar
• Nam EH, Lee Y, Park YK, Lee JW, Kim S. Zeb2 upregulates integrin alpha5 expression through cooperation with sp1 to induce invasion during epithelial-mesenchymal transition of human cancer cells. Carcinogenesis. 2012;33(3):563–571. doi:10.1093/carcin/bgs005.
   PubMed Web of Science ®Google Scholar
• Kouros-Mehr H, Bechis SK, Slorach EM, Littlepage LE, Egeblad M, Ewald AJ, Pai SY, Ho IC, Werb Z. Gata-3 links tumor differentiation and dissemination in a luminal breast cancer model. Cancer Cell. 2008;13(2):141–152. doi:10.1016/j.ccr.2008.01.011.
   PubMed Web of Science ®Google Scholar
• Yan W, Cao QJ, Arenas RB, Bentley B, Shao R. Gata3 inhibits breast cancer metastasis through the reversal of epithelial-mesenchymal transition. J Biol Chem. 2010;285(18):14042–14051. doi:10.1074/jbc.M110.105262.
   PubMed Web of Science ®Google Scholar
• Eastham AM, Spencer H, Soncin F, Ritson S, Merry CL, Stern PL, Ward CM. Epithelial-mesenchymal transition events during human embryonic stem cell differentiation. Cancer Res. 2007;67(23):11254–11262. doi:10.1158/0008-5472.CAN-07-2253.
   PubMed Web of Science ®Google Scholar
• Nawshad A, Lagamba D, Polad A, Hay ED. Transforming growth factor-beta signaling during epithelial-mesenchymal transformation: Implications for embryogenesis and tumor metastasis. Cells, Tissues, Organs. 2005;179(1-2):11–23. doi:10.1159/000084505.
   PubMed Web of Science ®Google Scholar
• Massague J. Tgf-beta signal transduction. Annu Rev Biochem. 1998;67:753–791. doi:10.1146/annurev.biochem.67.1.753.
   PubMed Web of Science ®Google Scholar
• Blokzijl A, ten Dijke P, Ibanez CF. Physical and functional interaction between gata-3 and smad3 allows tgf-beta regulation of gata target genes. Current biology: CB. 2002;12(1):35–45. doi:10.1016/S0960-9822(01)00623-6.
   PubMed Web of Science ®Google Scholar
• Tarasewicz E, Rivas L, Hamdan R, Dokic D, Parimi V, Bernabe BP, Thomas A, Shea LD, Jeruss JS. Inhibition of cdk-mediated phosphorylation of smad3 results in decreased oncogenesis in triple negative breast cancer cells. Cell Cycle. 2014;13(20):3191–3201. doi:10.4161/15384101.2014.950126.
   PubMed Web of Science ®Google Scholar
• O'Doherty U, Swiggard WJ, Malim MH. Human immunodeficiency virus type 1 spinoculation enhances infection through virus binding. J Virol. 2000;74(21):10074–10080. doi:10.1128/JVI.74.21.10074-10080.2000.
   PubMed Web of Science ®Google Scholar
• Williams RL, Hilton DJ, Pease S, Willson TA, Stewart CL, Gearing DP, Wagner EF, Metcalf D, Nicola NA, Gough NM. Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells. Nature. 1988;336(6200):684–687. doi:10.1038/336684a0.
   PubMed Web of Science ®Google Scholar
• Tagler D, Tu T, Smith RM, Anderson NR, Tingen CM, Woodruff TK, Shea LD. Embryonic fibroblasts enable the culture of primary ovarian follicles within alginate hydrogels. Tissue Eng Part A. 2012;18(11–12):1229–1238. doi:10.1089/ten.tea.2011.0418.
   PubMed Web of Science ®Google Scholar
• Shaw FL, Harrison H, Spence K, Ablett MP, Simoes BM, Farnie G, Clarke RB. A detailed mammosphere assay protocol for the quantification of breast stem cell activity. J Mammary Gland Biol Neoplasia. 2012;17(2):111–117. doi:10.1007/s10911-012-9255-3.
   PubMed Web of Science ®Google Scholar
• Miyoshi H, Blömer U, Takahashi M, Gage FH, Verma IM. Development of a self-inactivating lentivirus vector. J Virol. 1998;72(10):8150–8157.
   PubMed Web of Science ®Google Scholar
• Shin S, Shea LD. Lentivirus immobilization to nanoparticles for enhanced and localized delivery from hydrogels. Mol Ther. 2010;18(4):700–706. doi:10.1038/mt.2009.300.
   PubMed Web of Science ®Google Scholar
• Bernabé BP, Shin S, Rios PD, Broadbelt LJ, Shea LD, Seidlits SK. Dynamic transcription factor activity networks in response to independently altered mechanical and adhesive microenvironmental cues. Integr Biol. 2016;8(8):844–860.
   Google Scholar
• R Core Team. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2014.
   Google Scholar
• Smyth GK. Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol. 2004;3:(1):1544–6115. doi:10.2202/1544-6115.1027.
   PubMedGoogle Scholar
• Benjamini Y, Hochberg Y. Controlling the false discovery rate: A practical and powerful approach to multiple testing. Journal of the royal statistical society Series B (Methodological). 1995;57(1):289–300.
   Web of Science ®Google Scholar
• Wickham H. Ggplot2. Elegant graphics for data analysis. New York (NY):Springer Science + Business Media, LLC; 2009.
   Google Scholar