The latest research progress of effects of carcinoma-associated fibroblasts on breast cancer stem cells and its mechanism_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Bixiao , XI Chunfang ,  KANG Hua

Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, P. R. China;

Corresponding author：

KANG Hua, Email: kanghua@xwh.ccmu.edu.cn

Keywords：

breast cancer; cancer stem cell; fibroblast; epithelial mesenchymal transition; tumor microenvironment

DOI：

10.7507/1007-9424.201705032

Video：

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Objective To summarize research status and mechanism about effects of carcinoma-associated fibroblasts (CAFs) on breast cancer stem cells. Method Relevant literatures about the relationship between the CAFs and breast cancer stem cells were collected and reviewed. Results CAFs were the majority type of the breast cancer stromal cells. The cancer stromal cell was also the important part of the tumor microenvironment, which could promote the proliferation, adhesion, invasion, and metastasis of the breast cancer. A subpopulation of cancer stem cells with the potentials of self-renewal and multi-directional differentiation in the breast cancer tissues might cause the tumor development. There was a phenotypic heterogeneity in the beast cancer stem cells, it was related to the tumor recurrence and therapy resistance. The CAFs could promote the formation of breast cancer stem cells through the epithelial mesenchymal transition and promote the transformation of tumor stem cell phenotype. More research needed to be done to prove these processes. Conclusion CAFs play an important role in formation of breast cancer stem cells and transformation of tumor stem cell phenotype, which might provide a new idea about treating breast cancer.

Citation： WANG Bixiao, XI Chunfang, KANG Hua. The latest research progress of effects of carcinoma-associated fibroblasts on breast cancer stem cells and its mechanism. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2018, 25(1): 108-112. doi: 10.7507/1007-9424.201705032 Copy

1.	蔡成, 俞继卫, 姜波健. 肿瘤起始细胞及上皮-间质转化在肿瘤转移及耐药中的作用. 中国普外基础与临床杂志, 2013, 20(1): 99-103.
2.	Al-Hajj M, Wicha MS, Benito-Hernandez A, et al. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA, 2003, 100(7): 3983-3988.
3.	Ginestier C, Hur MH, Charafe-Jauffret E, 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.
4.	Chiotaki R, Polioudaki H, Theodoropoulos PA. Stem cell technology in breast cancer: current status and potential applications. Stem Cells Cloning, 2016, 9: 17-29.
5.	Vermeulen L, de Sousa e Melo F, Richel DJ, et al. The developing cancer stem-cell model: clinical challenges and opportunities. Lancet Oncol, 2012, 13(2): e83-e89.
6.	Liu S, Cong Y, Wang D, et al. Breast cancer stem cells transition between epithelial and mesenchymal states reflective of their normal counterparts. Stem Cell Reports, 2013, 2(1): 78-91.
7.	Dalerba P, Dylla SJ, Park IK, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA, 2007, 104(24): 10158-10163.
8.	Yachida S, Jones S, Bozic I, et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature, 2010, 467(7319): 1114-1117.
9.	赵宁, 傅深. 不同表型的乳腺癌干细胞研究现状及其临床应用价值. 中国癌症杂志, 2016, 26(8): 699-703.
10.	Cancer Genome Atlas Research Network, Weinstein JN, Collisson EA, et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet, 2013, 45(10): 1113-1120.
11.	Plaks V, Kong N, Werb Z. The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells? Cell Stem Cell, 2015, 16(3): 225-238.
12.	Korkaya H, Liu S, Wicha MS. Breast cancer stem cells, cytokine networks, and the tumor microenvironment. J Clin Invest, 2011, 121(10): 3804-3809.
13.	Liu S, Ginestier C, Ou SJ, et al. Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks. Cancer Res, 2011, 71(2): 614-624.
14.	Li K, Kang H, Wang Y, et al. Letrozole-induced functional changes in carcinoma-associated fibroblasts and their influence on breast cancer cell biology. Med Oncol, 2016, 33(7): 64.
15.	Gascard P, Tlsty TD. Carcinoma-associated fibroblasts: orchestrating the composition of malignancy. Genes Dev, 2016, 30(9): 1002-1019.
16.	Martinez-Outschoorn UE, Pavlides S, Whitaker-Menezes D, et al. Tumor cells induce the cancer associated fibroblast phenotype via caveolin-1 degradation: implications for breast cancer and DCIS therapy with autophagy inhibitors. Cell Cycle, 2010, 9(12): 2423-2433.
17.	Buchsbaum RJ, Oh SY. Breast cancer-associated fibroblasts: Where we are and where we need to go. Cancers (Basel), 2016, 8(2). pii: E19.
18.	Öhlund D, Elyada E, Tuveson D. Fibroblast heterogeneity in the cancer wound. J Exp Med, 2014, 211(8): 1503-1523.
19.	Pallangyo CK, Ziegler PK, Greten FR. IKKβ acts as a tumor suppressor in cancer-associated fibroblasts during intestinal tumorigenesis. J Exp Med, 2015, 212(13): 2253-2266.
20.	Koliaraki V, Pasparakis M, Kollias G. IKKβ in intestinal mesenchymal cells promotes initiation of colitis-associated cancer. J Exp Med, 2015, 212(13): 2235-2251.
21.	Wagner EF. Cancer: Fibroblasts for all seasons. Nature, 2016, 530(7588): 42-43.
22.	Bussard KM, Mutkus L, Stumpf K, et al. Tumor-associated stromal cells as key contributors to the tumor microenvironment. Breast Cancer Res, 2016, 18(1): 84.
23.	Luo M, Brooks M, Wicha MS. Epithelial-mesenchymal plasticity of breast cancer stem cells: implications for metastasis and therapeutic resistance. Curr Pharm Des, 2015, 21(10): 1301-1310.
24.	韩雅丽, 张晏文, 王琳琳, 等. 癌相关成纤维细胞促进肿瘤进展的复杂分子机制探讨. 癌症进展, 2016, 14(1): 36-39.
25.	Scheel C, Eaton EN, Li SH, et al. Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast. Cell, 2011, 145(6): 926-940.
26.	Chaffer CL, Marjanovic ND, Lee T, et al. Poised chromatin at the ZEB1 promoter enables breast cancer cell plasticity and enhances tumorigenicity. Cell, 2013, 154(1): 61-74.
27.	Giannoni E, Bianchini F, Masieri L, et al. Reciprocal activation of prostate cancer cells and cancer-associated fibroblasts stimulates epithelial-mesenchymal transition and cancer stemness. Cancer Res, 2010, 70(17): 6945-6956.
28.	McCuaig R, Wu F, Dunn J, et al. The biological and clinical significance of stromal-epithelial interactions in breast cancer. Pathology, 2017, 49(2): 133-140.
29.	Wolfson B, Eades G, Zhou Q. Adipocyte activation of cancer stem cellsignaling in breast cancer. World J Biol Chem, 2015, 6(2): 39-47.
30.	Korkaya H, Kim GI, Davis A, et al. Activation of an IL6 inflammatory loop mediates trastuzumab resistance in HER2+ breast cancer by expanding the cancer stem cell population. Mol Cell, 2012, 47(4): 570-584.
31.	Giordano C, Chemi F, Panza S, et al. Leptin as a mediator of tumor-stromal interactions promotes breast cancer stem cell activity. Oncotarget, 2016, 7(2): 1262-1275.
32.	Oskarsson T, Batlle E, Massagué J. Metastatic stem cells: sources, niches, and vital pathways. Cell Stem Cell, 2014, 14(3): 306-321.
33.	Zhang XH, Jin X, Malladi S, et al. Selection of bone metastasis seeds by mesenchymal signals in the primary tumor stroma. Cell, 2013, 154(5): 1060-1073.
34.	Erdogan B, Webb DJ. Cancer-associated fibroblasts modulate growth factor signaling and extracellular matrix remodeling to regulate tumor metastasis. Biochem Soc Trans, 2017, 45(1): 229-236.
35.	Oskarsson T, Acharyya S, Zhang XH, et al. Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs. Nat Med, 2011, 17(7): 867-874.
36.	Jung YY, Kim HM, Koo JS. The role of cancer-associated fibroblasts in breast cancer pathobiology. Histol Histopathol, 2016, 31(4): 371-378.
37.	Tchou J, Kossenkov AV, Chang L, et al. Human breast cancer associated fibroblasts exhibit subtype specific gene expression profiles. BMC Med Genomics, 2012, 5: 39.

1. 蔡成, 俞继卫, 姜波健. 肿瘤起始细胞及上皮-间质转化在肿瘤转移及耐药中的作用. 中国普外基础与临床杂志, 2013, 20(1): 99-103.
2. Al-Hajj M, Wicha MS, Benito-Hernandez A, et al. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA, 2003, 100(7): 3983-3988.
3. Ginestier C, Hur MH, Charafe-Jauffret E, 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.
4. Chiotaki R, Polioudaki H, Theodoropoulos PA. Stem cell technology in breast cancer: current status and potential applications. Stem Cells Cloning, 2016, 9: 17-29.
5. Vermeulen L, de Sousa e Melo F, Richel DJ, et al. The developing cancer stem-cell model: clinical challenges and opportunities. Lancet Oncol, 2012, 13(2): e83-e89.
6. Liu S, Cong Y, Wang D, et al. Breast cancer stem cells transition between epithelial and mesenchymal states reflective of their normal counterparts. Stem Cell Reports, 2013, 2(1): 78-91.
7. Dalerba P, Dylla SJ, Park IK, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA, 2007, 104(24): 10158-10163.
8. Yachida S, Jones S, Bozic I, et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature, 2010, 467(7319): 1114-1117.
9. 赵宁, 傅深. 不同表型的乳腺癌干细胞研究现状及其临床应用价值. 中国癌症杂志, 2016, 26(8): 699-703.
10. Cancer Genome Atlas Research Network, Weinstein JN, Collisson EA, et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet, 2013, 45(10): 1113-1120.
11. Plaks V, Kong N, Werb Z. The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells? Cell Stem Cell, 2015, 16(3): 225-238.
12. Korkaya H, Liu S, Wicha MS. Breast cancer stem cells, cytokine networks, and the tumor microenvironment. J Clin Invest, 2011, 121(10): 3804-3809.
13. Liu S, Ginestier C, Ou SJ, et al. Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks. Cancer Res, 2011, 71(2): 614-624.
14. Li K, Kang H, Wang Y, et al. Letrozole-induced functional changes in carcinoma-associated fibroblasts and their influence on breast cancer cell biology. Med Oncol, 2016, 33(7): 64.
15. Gascard P, Tlsty TD. Carcinoma-associated fibroblasts: orchestrating the composition of malignancy. Genes Dev, 2016, 30(9): 1002-1019.
16. Martinez-Outschoorn UE, Pavlides S, Whitaker-Menezes D, et al. Tumor cells induce the cancer associated fibroblast phenotype via caveolin-1 degradation: implications for breast cancer and DCIS therapy with autophagy inhibitors. Cell Cycle, 2010, 9(12): 2423-2433.
17. Buchsbaum RJ, Oh SY. Breast cancer-associated fibroblasts: Where we are and where we need to go. Cancers (Basel), 2016, 8(2). pii: E19.
18. Öhlund D, Elyada E, Tuveson D. Fibroblast heterogeneity in the cancer wound. J Exp Med, 2014, 211(8): 1503-1523.
19. Pallangyo CK, Ziegler PK, Greten FR. IKKβ acts as a tumor suppressor in cancer-associated fibroblasts during intestinal tumorigenesis. J Exp Med, 2015, 212(13): 2253-2266.
20. Koliaraki V, Pasparakis M, Kollias G. IKKβ in intestinal mesenchymal cells promotes initiation of colitis-associated cancer. J Exp Med, 2015, 212(13): 2235-2251.
21. Wagner EF. Cancer: Fibroblasts for all seasons. Nature, 2016, 530(7588): 42-43.
22. Bussard KM, Mutkus L, Stumpf K, et al. Tumor-associated stromal cells as key contributors to the tumor microenvironment. Breast Cancer Res, 2016, 18(1): 84.
23. Luo M, Brooks M, Wicha MS. Epithelial-mesenchymal plasticity of breast cancer stem cells: implications for metastasis and therapeutic resistance. Curr Pharm Des, 2015, 21(10): 1301-1310.
24. 韩雅丽, 张晏文, 王琳琳, 等. 癌相关成纤维细胞促进肿瘤进展的复杂分子机制探讨. 癌症进展, 2016, 14(1): 36-39.
25. Scheel C, Eaton EN, Li SH, et al. Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast. Cell, 2011, 145(6): 926-940.
26. Chaffer CL, Marjanovic ND, Lee T, et al. Poised chromatin at the ZEB1 promoter enables breast cancer cell plasticity and enhances tumorigenicity. Cell, 2013, 154(1): 61-74.
27. Giannoni E, Bianchini F, Masieri L, et al. Reciprocal activation of prostate cancer cells and cancer-associated fibroblasts stimulates epithelial-mesenchymal transition and cancer stemness. Cancer Res, 2010, 70(17): 6945-6956.
28. McCuaig R, Wu F, Dunn J, et al. The biological and clinical significance of stromal-epithelial interactions in breast cancer. Pathology, 2017, 49(2): 133-140.
29. Wolfson B, Eades G, Zhou Q. Adipocyte activation of cancer stem cellsignaling in breast cancer. World J Biol Chem, 2015, 6(2): 39-47.
30. Korkaya H, Kim GI, Davis A, et al. Activation of an IL6 inflammatory loop mediates trastuzumab resistance in HER2+ breast cancer by expanding the cancer stem cell population. Mol Cell, 2012, 47(4): 570-584.
31. Giordano C, Chemi F, Panza S, et al. Leptin as a mediator of tumor-stromal interactions promotes breast cancer stem cell activity. Oncotarget, 2016, 7(2): 1262-1275.
32. Oskarsson T, Batlle E, Massagué J. Metastatic stem cells: sources, niches, and vital pathways. Cell Stem Cell, 2014, 14(3): 306-321.
33. Zhang XH, Jin X, Malladi S, et al. Selection of bone metastasis seeds by mesenchymal signals in the primary tumor stroma. Cell, 2013, 154(5): 1060-1073.
34. Erdogan B, Webb DJ. Cancer-associated fibroblasts modulate growth factor signaling and extracellular matrix remodeling to regulate tumor metastasis. Biochem Soc Trans, 2017, 45(1): 229-236.
35. Oskarsson T, Acharyya S, Zhang XH, et al. Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs. Nat Med, 2011, 17(7): 867-874.
36. Jung YY, Kim HM, Koo JS. The role of cancer-associated fibroblasts in breast cancer pathobiology. Histol Histopathol, 2016, 31(4): 371-378.
37. Tchou J, Kossenkov AV, Chang L, et al. Human breast cancer associated fibroblasts exhibit subtype specific gene expression profiles. BMC Med Genomics, 2012, 5: 39.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

The latest research progress of effects of carcinoma-associated fibroblasts on breast cancer stem cells and its mechanism

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