A functional in vitro model of heterotypic interactions reveals a role for interferon-positive carcinoma associated fibroblasts in breast cancer

详细信息    查看全文

• 作者：Abdel Nasser Hosein ; Julie Livingstone ; Marguerite Buchanan ; James F Reid…
• 关键词：Stroma ; Carcinoma ; associated fibroblasts ; Breast cancer ; Interferon
• 刊名：BMC Cancer
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：15
• 期：1
• 全文大小：3,522 KB
• 参考文献：1. Hanahan, D, Weinberg, RA (2000) The hallmarks of cancer. Cell 100: pp. 57-70 CrossRef
  2. Hanahan, D, Weinberg, RA (2011) Hallmarks of cancer: the next generation. Cell 144: pp. 646-74 CrossRef
  3. Finak, G, Bertos, N, Pepin, F, Sadekova, S, Souleimanova, M, Zhao, H (2008) Stromal gene expression predicts clinical outcome in breast cancer. Nat Med 14: pp. 518-27 CrossRef
  4. Farmer, P, Bonnefoi, H, Anderle, P, Cameron, D, Wirapati, P, Becette, V (2009) A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer. Nat Med 15: pp. 68-74 CrossRef
  5. Kalluri, R, Zeisberg, M (2006) Fibroblasts in cancer. Nat Rev Cancer 6: pp. 392-401 CrossRef
  6. Madar, S, Harel, E, Goldstein, I, Stein, Y, Kogan-Sakin, I, Kamer, I (2013) Mutant p53 attenuates the anti-tumorigenic activity of fibroblasts-secreted interferon beta. PLoS One 8: pp. e61353 CrossRef
  7. Bhowmick, NA, Chytil, A, Plieth, D, Gorska, AE, Dumont, N, Shappell, S (2004) TGF-beta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia. Science 303: pp. 848-51 CrossRef
  8. Orimo, A, Gupta, PB, Sgroi, DC, Arenzana-Seisdedos, F, Delaunay, T, Naeem, R (2005) Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 121: pp. 335-48 CrossRef
  9. Kojima, Y, Acar, A, Eaton, EN, Mellody, KT, Scheel, C, Ben-Porath, I (2010) Autocrine TGF-beta and stromal cell-derived factor-1 (SDF-1) signaling drives the evolution of tumor-promoting mammary stromal myofibroblasts. Proc Natl Acad Sci U S A 107: pp. 20009-14 CrossRef
  10. Adams, EF, Newton, CJ, Braunsberg, H, Shaikh, N, Ghilchik, M, James, VH (1988) Effects of human breast fibroblasts on growth and 17 beta-estradiol dehydrogenase activity of MCF-7 cells in culture. Breast Cancer Res Treat 11: pp. 165-72 CrossRef
  11. Roozendaal, KE, Klijn, JG, Ooijen, B, Claassen, C, Eggermont, AM, Henzen-Logmans, SC (1996) Differential regulation of breast tumor cell proliferation by stromal fibroblasts of various breast tissue sources. Int J Cancer 65: pp. 120-5 CrossRef
  12. Dong-Le Bourhis, X, Berthois, Y, Millot, G, Degeorges, A, Sylvi, M, Martin, PM (1997) Effect of stromal and epithelial cells derived from normal and tumorous breast tissue on the proliferation of human breast cancer cell lines in co-culture. Int J Cancer 71: pp. 42-8 CrossRef
  13. Buess, M, Nuyten, DS, Hastie, T, Nielsen, T, Pesich, R, Brown, PO (2007) Characterization of heterotypic interaction effects in vitro to deconvolute global gene expression profiles in cancer. Genome Biol 8: pp. R191 CrossRef
  14. Vijver, MJ, He, YD, Veer, LJ, Dai, H, Hart, AA, Voskuil, DW (2002) A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 347: pp. 1999-2009 CrossRef
  15. Hosein, AN, Wu, M, Arcand, SL, Lavallee, S, Hebert, J, Tonin, PN (2010) Breast carcinoma-associated fibroblasts rarely contain p53 mutations or chromosomal aberrations. Cancer Res 70: pp. 5770-7 CrossRef
  16. Sorlie, T, Tibs
• 刊物主题：Cancer Research; Oncology; Stem Cells; Animal Models; Internal Medicine;
• 出版者：BioMed Central
• ISSN：1471-2407

文摘

Background Cancer-associated fibroblasts (CAFs) play an important role in breast cancer pathogenesis by paracrine regulation of breast cancer cell biology. Several in vitro and mouse models have characterized the role of cell contact and cytokine molecules mediating this relationship, although few reports have used human CAFs from breast tumors. Methods Primary breast CAF cultures were established and gene expression profiles analysed in order to guide subsequent co-culture models. We used a combination of colorimetric proliferation assays and gene expression profiling to determine the effect of CAFs on the MCF-7 breast cancer cell in an indirect co-culture system. Results Using gene expression profiling, we found that a subgroup of breast CAFs are positive for a type one interferon response, confirming previous reports of an activated type one interferon response in whole tumor datasets. Interferon positive breast cancer patients show a poor prognostic outcome in an independent microarray dataset. In addition, CAFs positive for the type one interferon response promoted the growth of the MCF-7 breast cancer cell line in an indirect co-culture model. The addition of a neutralizing antibody against the ligand mediating the type one response in fibroblasts, interferon-β, reverted this co-culture phenotype. CAFs not expressing the interferon response genes also promoted the growth of the MCF-7 breast cancer cell line but this phenotype was independent of the type one fibroblast interferon ligand. Conclusions Primary breast CAFs show inter-patient molecular heterogeneity as evidenced by interferon response gene elements activated in a subgroup of CAFs, which result in paracrine pro-proliferative effects in a breast cancer cell line co-culture model.