Expression of Stromal Cell-Derived Factor-1 and Its Relation with Prognosis in Human Breast Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

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Stromal cell-derived factor-1 Breast cancer Prognosis

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【Abstract】Objective Stromal cell-derived factor-1(SDF-1, CXCL12) is a member of the CXC subfamily of chemokines which, through its cognate receptor (CXCR4), plays an important role in tumor invasion and metastasis. This study analyzed quantitatively the expression of SDF-1 and its relation with clinicopathologic feature and clinical outcome in human breast cancer.
Methods Expression of SDF-1 mRNA in 8 breast cancer cell lines, an endothelial cell line HECV and a fibroblast cell MRC5 was studied by using RT-PCR. In addition, the expression of SDF-1 was investigated at both protein (immunohistochemistry) and mRNA(real-time PCR) levels in a group of human normal mammary(n=32) and tumour tissues(n=120).
Results SDF-1 expression was identified in MRC5, MDA-MB435s, MDA-MB436, MCF7 cell lines, breast tumour and normal tissues. Significantly higher level of SDF-1 was seen in lymph node positive than in lymph node negative tumours (399.00±210.00 vs 0.89±0.47), P=0.048. The level of SDF-1 expression in patients who developed local recurrence or metastasis, or patients who died of breast cancer was higher than in patients who were disease free as well, (670.00±346.00 vs 0.83±0.35), P=0.01. It was most notable that level of SDF-1 was significantly correlated with over survival (P=0.01) and incidence free survival (P=0.035, by Cox proportion analysis).
Conclusion SDF-1 is a factor that is expressed in both stromal cells and some breast cancer cells. Its level are correlated with lymph node involvement, prognosis and survival in patients with breast cancer. SDF-1 may therefore have a potential prognostic value in breast cancer.

Citation： KANG Hua,Robert E Mansel,Wen G Jiang.. Expression of Stromal Cell-Derived Factor-1 and Its Relation with Prognosis in Human Breast Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2005, 12(5): 483-487. doi: Copy

1.	Phillips RJ, Burdick MD, Lutz M, et al. The stromal derived factor1/CXCL12CXC chemokine receptor 4 biological axis in nonsmall cell lung cancer metastases [Ｊ]. Am J Respir Crit Care Med， 2003; 167(12)∶1676.
2.	Geminder H, SagiAssif O, Goldberg L, et al. A possible role for CXCR4 and its ligand, the CXC chemokine stromal cellderived factor1, in the development of bone marrow metastases in neuroblastoma [Ｊ]. J Immunol, 2001; 167(8)∶4747.
3.	Nagasawa T, Kikutani H, Kishimoto T. Molecular cloning and structure of a preBcell growthstimulating factor [Ｊ]. Proc Natl Acad Sci USA, 1994; 91(6)∶2305.
4.	Nagasawa T, Tachibana K, Kishimoto T. A novel CXC chemokine PBSF/SDF1 and its receptor CXCR4: their functions in development, hematopoiesis and HIV infection [Ｊ]. Semin Immunol, 1998; 10(3)∶179.
5.	Fernandis AZ, Prasad A, Band H, et al. Regulation of CXCR4mediated chemotaxis and chemoinvasion of breast cancer cells [Ｊ]. Oncogene, 2004; 23(1)∶157.
6.	Muller A, Homey B, Soto H, et al. Involvement of chemokine receptors in breast cancer metastasis [Ｊ]. Nature, 2001; 410(6824)∶50.
7.	Jiang WG, DouglasJones A, Mansel RE. Expression of peroxisomeproliferator activated receptorgamma (PPARgamma) and the PPARgamma coactivator, PGC1, in human breast cancer correlates with clinical outcomes [Ｊ]. Int J Cancer, 2003; 106(5)∶752.
8.	Jiang WG, Watkins G, Lane J, et al. Prognostic value of rho GTPases and rho guanine nucleotide dissociation inhibitors in human breast cancers [Ｊ]. Clin Cancer Res, 2003; 9(17)∶6432.
9.	Galea MH, Blamey RW, Elston CE, et al. The Nottingham Prognostic Index in primary breast cancer [Ｊ]. Breast Res Treat, 1992; 22(3)∶207.
10.	Yun HJ, Jo DY. Production of stromal cellderived factor1 (SDF1)and expression of CXCR4 in human bone marrow endothelial cells [Ｊ]. J Korean Med Sci, 2003; 18(5)∶679.
11.	Koshiba T, Hosotani R, Miyamoto Y, et al. Expression of stromal cellderived factor 1 and CXCR4 ligand receptor system in pancreatic cancer: a possible role for tumor progression [Ｊ]. Clin Cancer Res, 2000; 6(9)∶3530.
12.	Uchida D, Begum NM, Almofti A, et al. Possible role of stromalcellderived factor1/CXCR4 signaling on lymph node metastasis of oral squamous cell carcinoma [Ｊ]. Exp Cell Res, 2003; 290(2)∶289.
13.	Fedyk ER, Jones D, Critchley HO, et al. Expression of stromalderived factor1 is decreased by IL1 and TNF and in dermal wound healing [Ｊ]. J Immunol, 2001; 166(9)∶5749.
14.	Hall JM, Korach KS. Stromal cellderived factor 1, a novel target of estrogen receptor action, mediates the mitogenic effects of estradiol in ovarian and breast cancer cells [Ｊ]. Mol Endocrinol, 2003; 17(5)∶792.
15.	Kang H, Mansel RE, Jiang WG. Genetic manipulation of stromal cellderived factor1 attests the pivotal role of the autocrine SDF1CXCR4 pathway in the aggressivenss of breast cancer cells [Ｊ]. Int J Oncol, 2005; 26(5)∶1429.
16.	Kato M, Kitayama J, Kazama S, et al. Expression pattern of CXC chemokine receptor4 is correlated with lymph node metastasis in human invasive ductal carcinoma [Ｊ]. Breast Cancer, Res, 2003; 5(5)∶144.

1. Phillips RJ, Burdick MD, Lutz M, et al. The stromal derived factor1/CXCL12CXC chemokine receptor 4 biological axis in nonsmall cell lung cancer metastases [Ｊ]. Am J Respir Crit Care Med， 2003; 167(12)∶1676.
2. Geminder H, SagiAssif O, Goldberg L, et al. A possible role for CXCR4 and its ligand, the CXC chemokine stromal cellderived factor1, in the development of bone marrow metastases in neuroblastoma [Ｊ]. J Immunol, 2001; 167(8)∶4747.
3. Nagasawa T, Kikutani H, Kishimoto T. Molecular cloning and structure of a preBcell growthstimulating factor [Ｊ]. Proc Natl Acad Sci USA, 1994; 91(6)∶2305.
4. Nagasawa T, Tachibana K, Kishimoto T. A novel CXC chemokine PBSF/SDF1 and its receptor CXCR4: their functions in development, hematopoiesis and HIV infection [Ｊ]. Semin Immunol, 1998; 10(3)∶179.
5. Fernandis AZ, Prasad A, Band H, et al. Regulation of CXCR4mediated chemotaxis and chemoinvasion of breast cancer cells [Ｊ]. Oncogene, 2004; 23(1)∶157.
6. Muller A, Homey B, Soto H, et al. Involvement of chemokine receptors in breast cancer metastasis [Ｊ]. Nature, 2001; 410(6824)∶50.
7. Jiang WG, DouglasJones A, Mansel RE. Expression of peroxisomeproliferator activated receptorgamma (PPARgamma) and the PPARgamma coactivator, PGC1, in human breast cancer correlates with clinical outcomes [Ｊ]. Int J Cancer, 2003; 106(5)∶752.
8. Jiang WG, Watkins G, Lane J, et al. Prognostic value of rho GTPases and rho guanine nucleotide dissociation inhibitors in human breast cancers [Ｊ]. Clin Cancer Res, 2003; 9(17)∶6432.
9. Galea MH, Blamey RW, Elston CE, et al. The Nottingham Prognostic Index in primary breast cancer [Ｊ]. Breast Res Treat, 1992; 22(3)∶207.
10. Yun HJ, Jo DY. Production of stromal cellderived factor1 (SDF1)and expression of CXCR4 in human bone marrow endothelial cells [Ｊ]. J Korean Med Sci, 2003; 18(5)∶679.
11. Koshiba T, Hosotani R, Miyamoto Y, et al. Expression of stromal cellderived factor 1 and CXCR4 ligand receptor system in pancreatic cancer: a possible role for tumor progression [Ｊ]. Clin Cancer Res, 2000; 6(9)∶3530.
12. Uchida D, Begum NM, Almofti A, et al. Possible role of stromalcellderived factor1/CXCR4 signaling on lymph node metastasis of oral squamous cell carcinoma [Ｊ]. Exp Cell Res, 2003; 290(2)∶289.
13. Fedyk ER, Jones D, Critchley HO, et al. Expression of stromalderived factor1 is decreased by IL1 and TNF and in dermal wound healing [Ｊ]. J Immunol, 2001; 166(9)∶5749.
14. Hall JM, Korach KS. Stromal cellderived factor 1, a novel target of estrogen receptor action, mediates the mitogenic effects of estradiol in ovarian and breast cancer cells [Ｊ]. Mol Endocrinol, 2003; 17(5)∶792.
15. Kang H, Mansel RE, Jiang WG. Genetic manipulation of stromal cellderived factor1 attests the pivotal role of the autocrine SDF1CXCR4 pathway in the aggressivenss of breast cancer cells [Ｊ]. Int J Oncol, 2005; 26(5)∶1429.
16. Kato M, Kitayama J, Kazama S, et al. Expression pattern of CXC chemokine receptor4 is correlated with lymph node metastasis in human invasive ductal carcinoma [Ｊ]. Breast Cancer, Res, 2003; 5(5)∶144.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression of Stromal Cell-Derived Factor-1 and Its Relation with Prognosis in Human Breast Cancer

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