Research Status and Biological Characteristics of Stromal Fibroblast in Breast Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Xiaoyao , KANG Hua.

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

Corresponding author：

Keywords：

Breast cancer; Stroma; Fibroblasts; Biological characteristics; Research status

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ObjectiveTo summarize the research status and biological characteristics of stromal fibroblast in breast cancer. MethodsRelevant literatures about the breast cancer stromal fibroblasts published recently were collected and reviewed. ResultsIn addition to cancer cells, breast cancer included stromal cells. The fibroblasts were the major components of breast cancer stromal, which had significantly different biological characteristics from normal fibroblasts. The fibroblasts were characterized by α-SMA positive, p53 gene mutation, secretion of various cytokines or chemokines in addition to the production of collagen substances, involving in breast cancer growth, migration, invasion and metastasis through a variety of signaling pathways. ConclusionThe biological characteristics of stromal fibroblasts in breast cancer may reflect lesion properties, be of great importance to diagnosis and differential diagnosis and prognosis prediction of breast cancer. More attentions will be paid to the target therapy for stromal fibroblasts in breast cancer.

Citation： ZHANG Xiaoyao,KANG Hua.. Research Status and Biological Characteristics of Stromal Fibroblast in Breast Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(2): 212-215. doi: Copy

1.	Sappino AP, Skalli O, Jackson B, et al. Smoothmuscle differentiation in stromal cells of malignant and nonmalignant breast tissues [J]. Int J Cancer, 1988, 41(5): 707712.
2.	KunzSchughart LA, Knuechel R. Tumorassociated fibroblasts (part I): Active stromal participants in tumor development and progression? [J]. Histol Histopathol, 2002, 17(2): 599621.
3.	Hasebe T, Okada N, Tamura N, et al. P53 expression in tumor stromal fibroblasts is associated with the outcome of patients with invasive ductal carcinoma of the breast [J] Cancer Sci, 2009, 100(11): 21012108.
4.	RnnovJessen L, Celis JE, Van Deurs B, et al. A fibroblastassociated antigen: characterization in fibroblasts and immunoreactivity in smooth muscle differentiated stromal cells [J]. J Histochem Cytochem, 1992, 40 (4): 475486.
5.	Petersen OW, Nielsen HL, Gudjonsson T, et al. Epithelial to mesenchymal transition in human breast cancer can provide a nonmalignant stroma [J]. Am J pathol, 2003, 162 (2): 391402.
6.	Direkze NC, HodivalaDilke K, Jeffery R, et al. Bone marrow contribution to tumorassociated myofibroblasts and fibroblasts [J]. Cancer Res, 2004, 64(23): 84928495.
7.	RnnovJessen L, Petersen OW, Koteliansky VE, et al. The origin of the myofibroblasts in breast cancer. Recapitulation of tumor environment in culture unravels diversity and implicates converted fibroblasts and recruited smooth muscle cells [J]. J Clin Invest, 1995, 95(2): 859873.
8.	吴克复. 肿瘤微环境与细胞生态学导论 [M]. 北京: 科学出版社, 2009: 141.
9.	黄桂林, 张剑权, 吴毅平, 等. 新辅助化疗对乳腺癌患者胰岛素样生长因子1受体表达的影响 [J]. 中国普外基础与临床杂志, 2009, 16(10): 834837.
10.	Kang H, Watkins G, Parr C, et al. Stromal cell derived factor1: its influence on invasiveness and migration of breast cancer cells in vitro, and its association with prognosis and survival in human breast cancer [J]. Breast Cancer Res, 2005, 7(4): R402R410.
11.	Orimo A, Gupta PB, Sgroi DC, et al. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF1/CXCL12 secretion [J]. Cell, 2005, 121(3): 335348.
12.	蔡伟, 刘丹丹, 康骅, 等. ET方案新辅助化疗对乳腺癌组织中CXCR4表达的影响及临床意义 [J]. 中国普外基础与临床杂志, 2010, 17(8): 812815, 823.
13.	Galiè M, Sorrentino C, Montani M, et al. Mammary carcinoma provides highly tumourigenic and invasive reactive stromal cells [J]. Carcinogenesis, 2005, 26(11): 18681878.
14.	Lieubeau B, Heymann MF, Henry F, et al. Immunomodulatory effects of tumorassociated fibroblasts in colorectaltumor development. [J] Int J Cancer, 1999, 81(4): 629636.
15.	Liao D, Luo Y , Markowitz D, et al. Cancer associated fibroblasts promote tumor growth and metastasis by modulating the tumor immune microenvironment in a 4T1 murine breast cancer model [J]. PLoS One, 2009, 4(11): e7965.
16.	Shekhar MP, Werdell J, Santner SJ, et al. Breast stroma plays a dominant regulatory role in breast epithelial growth and differentiation: implications for tumor development and progression [J]. Cancer Res, 2001, 61(4): 13201326.
17.	Pauley RJ, Santner SJ, Tait LR, et al. Regulated CYP19 aromatase transcription in breast stromal fibroblasts [J]. J Clin Endocrinol Metab, 2000, 85(2): 837846.
18.	Reed MJ, Purohit A. Breast cancer and the role of cytokines in regulating estrogen synthesis: an emerging hypothesis [J]. Endocr Rev, 1997, 18(5): 701715.
19.	Sasano H, Harada N. Intratumoral aromatase in human breast, endometrial, and ovarian malignancies [J]. Endocr Rev, 1998, 19(5): 593607.
20.	WalterYohrling J, Pratt BM, Ledbetter S, et al. Myofibroblasts enable invasion of endothelial cells into threedimensional tumor cell clusters: a novel in vitro tumor model [J]. Cancer Chemother Pharmacol, 2003, 52(4): 263269.
21.	Cancemi P, Albanese NN, DiCara G, et al. Multiple changes induced by fibroblasts on breast cancer cells [J]. Connect Tissue Res, 2010, 51(2): 88104.
22.	Singer CF, GschwantlerKaulich D, FinkRetter A, et al. Differential gene expression profile in breast cancerderived stromal fibroblasts [J]. Breast Cancer Res Treat, 2008, 110(2): 273281.
23.	赵新, 许焕丽, 唐伟, 等. 新型基质金属蛋白酶抑制剂LY52对肝癌细胞株MMPs表达及体外侵袭能力的影响 [J]. 中国普外基础与临床杂志, 2010, 17(8): 798802.
24.	Eck SM, Cté AL, Winkelman WD, et al. CXCR4 and MMP1 are elevated in breast carcinomaassociated fibroblasts and in normal mammary fibroblasts exposed to factors secreted by breast cancer cells [J]. Mol Cancer Res, 2009, 7(7): 10331044.
25.	Del Casar JM, González LO, Alvarez E, et al. Comparative analysis and clinical value of the expression of metalloproteases and their inhibitors by intratumor stromal fibroblasts and those at the invasive front of breast carcinomas [J]. Breast Cancer Res Treat, 2009, 116(1): 3952.
26.	Surowiak P, Suchocki S, Gyrffy B, et al. Stromal myofibroblasts in breast cancer: relations between their occurrence, tumor grade and expression of some tumour markers [J]. Folia Histochem Cytobiol, 2006, 44(2): 111116.
27.	Micke P, Ostman A. Tumourstroma interaction: cancer associated fibroblasts as novel targets in anti cancer therapy? [J]. Lung Cancer, 2004, 45 Suppl 2: S163S175.
28.	Kim Y, Wallace J, Li F, et al. Transformed epithelial cells and fibroblasts/myofibroblasts interaction in breast tumor: a mathematical model and experiments [J]. J Math Biol, 2010, 61(3): 401421.

1. Sappino AP, Skalli O, Jackson B, et al. Smoothmuscle differentiation in stromal cells of malignant and nonmalignant breast tissues [J]. Int J Cancer, 1988, 41(5): 707712.
2. KunzSchughart LA, Knuechel R. Tumorassociated fibroblasts (part I): Active stromal participants in tumor development and progression? [J]. Histol Histopathol, 2002, 17(2): 599621.
3. Hasebe T, Okada N, Tamura N, et al. P53 expression in tumor stromal fibroblasts is associated with the outcome of patients with invasive ductal carcinoma of the breast [J] Cancer Sci, 2009, 100(11): 21012108.
4. RnnovJessen L, Celis JE, Van Deurs B, et al. A fibroblastassociated antigen: characterization in fibroblasts and immunoreactivity in smooth muscle differentiated stromal cells [J]. J Histochem Cytochem, 1992, 40 (4): 475486.
5. Petersen OW, Nielsen HL, Gudjonsson T, et al. Epithelial to mesenchymal transition in human breast cancer can provide a nonmalignant stroma [J]. Am J pathol, 2003, 162 (2): 391402.
6. Direkze NC, HodivalaDilke K, Jeffery R, et al. Bone marrow contribution to tumorassociated myofibroblasts and fibroblasts [J]. Cancer Res, 2004, 64(23): 84928495.
7. RnnovJessen L, Petersen OW, Koteliansky VE, et al. The origin of the myofibroblasts in breast cancer. Recapitulation of tumor environment in culture unravels diversity and implicates converted fibroblasts and recruited smooth muscle cells [J]. J Clin Invest, 1995, 95(2): 859873.
8. 吴克复. 肿瘤微环境与细胞生态学导论 [M]. 北京: 科学出版社, 2009: 141.
9. 黄桂林, 张剑权, 吴毅平, 等. 新辅助化疗对乳腺癌患者胰岛素样生长因子1受体表达的影响 [J]. 中国普外基础与临床杂志, 2009, 16(10): 834837.
10. Kang H, Watkins G, Parr C, et al. Stromal cell derived factor1: its influence on invasiveness and migration of breast cancer cells in vitro, and its association with prognosis and survival in human breast cancer [J]. Breast Cancer Res, 2005, 7(4): R402R410.
11. Orimo A, Gupta PB, Sgroi DC, et al. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF1/CXCL12 secretion [J]. Cell, 2005, 121(3): 335348.
12. 蔡伟, 刘丹丹, 康骅, 等. ET方案新辅助化疗对乳腺癌组织中CXCR4表达的影响及临床意义 [J]. 中国普外基础与临床杂志, 2010, 17(8): 812815, 823.
13. Galiè M, Sorrentino C, Montani M, et al. Mammary carcinoma provides highly tumourigenic and invasive reactive stromal cells [J]. Carcinogenesis, 2005, 26(11): 18681878.
14. Lieubeau B, Heymann MF, Henry F, et al. Immunomodulatory effects of tumorassociated fibroblasts in colorectaltumor development. [J] Int J Cancer, 1999, 81(4): 629636.
15. Liao D, Luo Y , Markowitz D, et al. Cancer associated fibroblasts promote tumor growth and metastasis by modulating the tumor immune microenvironment in a 4T1 murine breast cancer model [J]. PLoS One, 2009, 4(11): e7965.
16. Shekhar MP, Werdell J, Santner SJ, et al. Breast stroma plays a dominant regulatory role in breast epithelial growth and differentiation: implications for tumor development and progression [J]. Cancer Res, 2001, 61(4): 13201326.
17. Pauley RJ, Santner SJ, Tait LR, et al. Regulated CYP19 aromatase transcription in breast stromal fibroblasts [J]. J Clin Endocrinol Metab, 2000, 85(2): 837846.
18. Reed MJ, Purohit A. Breast cancer and the role of cytokines in regulating estrogen synthesis: an emerging hypothesis [J]. Endocr Rev, 1997, 18(5): 701715.
19. Sasano H, Harada N. Intratumoral aromatase in human breast, endometrial, and ovarian malignancies [J]. Endocr Rev, 1998, 19(5): 593607.
20. WalterYohrling J, Pratt BM, Ledbetter S, et al. Myofibroblasts enable invasion of endothelial cells into threedimensional tumor cell clusters: a novel in vitro tumor model [J]. Cancer Chemother Pharmacol, 2003, 52(4): 263269.
21. Cancemi P, Albanese NN, DiCara G, et al. Multiple changes induced by fibroblasts on breast cancer cells [J]. Connect Tissue Res, 2010, 51(2): 88104.
22. Singer CF, GschwantlerKaulich D, FinkRetter A, et al. Differential gene expression profile in breast cancerderived stromal fibroblasts [J]. Breast Cancer Res Treat, 2008, 110(2): 273281.
23. 赵新, 许焕丽, 唐伟, 等. 新型基质金属蛋白酶抑制剂LY52对肝癌细胞株MMPs表达及体外侵袭能力的影响 [J]. 中国普外基础与临床杂志, 2010, 17(8): 798802.
24. Eck SM, Cté AL, Winkelman WD, et al. CXCR4 and MMP1 are elevated in breast carcinomaassociated fibroblasts and in normal mammary fibroblasts exposed to factors secreted by breast cancer cells [J]. Mol Cancer Res, 2009, 7(7): 10331044.
25. Del Casar JM, González LO, Alvarez E, et al. Comparative analysis and clinical value of the expression of metalloproteases and their inhibitors by intratumor stromal fibroblasts and those at the invasive front of breast carcinomas [J]. Breast Cancer Res Treat, 2009, 116(1): 3952.
26. Surowiak P, Suchocki S, Gyrffy B, et al. Stromal myofibroblasts in breast cancer: relations between their occurrence, tumor grade and expression of some tumour markers [J]. Folia Histochem Cytobiol, 2006, 44(2): 111116.
27. Micke P, Ostman A. Tumourstroma interaction: cancer associated fibroblasts as novel targets in anti cancer therapy? [J]. Lung Cancer, 2004, 45 Suppl 2: S163S175.
28. Kim Y, Wallace J, Li F, et al. Transformed epithelial cells and fibroblasts/myofibroblasts interaction in breast tumor: a mathematical model and experiments [J]. J Math Biol, 2010, 61(3): 401421.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research Status and Biological Characteristics of Stromal Fibroblast in Breast Cancer

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