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Breast Cancer Research
Published in: Breast Cancer Research 4/2005

Open Access 01-08-2005 | Research article

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

Authors: Hua Kang, Gareth Watkins, Christian Parr, Anthony Douglas-Jones, Robert E Mansel, Wen G Jiang

Published in: Breast Cancer Research | Issue 4/2005

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Abstract

Introduction

Stromal cell-derived factor (SDF)-1 (CXC chemokine ligand-12) is a member of the CXC subfamily of chemokines, which, through its cognate receptor (CXC chemokine receptor [CXCR]4), plays an important role in chemotaxis of cancer cells and in tumour metastasis. We conducted the present study to evaluate the effect of SDF-1 on the invasiveness and migration of breast cancer cells, and we analyzed the expression of SDF-1 and its relation to clinicopathological features and clinical outcomes in human breast cancer.

Method

Expression of SDF-1 mRNA in breast cancer, endothelial (HECV) and fibroblast (MRC5) cell lines and in human breast tissues were studied using RT-PCR. MDA-MB-231 cells were transfected with a SDF-1 expression vector, and their invasiveness and migration was tested in vitro. In addition, the expression of SDF-1 was investigated using immunohistochemistry and quantitative RT-PCR in samples of normal human mammary tissue (n = 32) and mammary tumour (n = 120).

Results

SDF-1 expression was identified in MRC5, MDA-MB-435s and MDA-MB-436 cell lines, but CXCR4 expression was detected in all cell lines and breast tissues. An autocrine loop was created following transfection of MDA-MB-231 (which was CXCR4 positive and SDF-1 negative) with a mammalian expression cassette encoding SDF-1 (MDA-MB-231SDF1+/+) or with control plasmid pcDNA4/GFP (MDA-MB-231+/-). MDA-MB-231SDF1+/+ cells exhibited significantly greater invasion and migration potential (in transfected cells versus in wild type and empty MDA-MB-231+/-; P < 0.01). In mammary tissues SDF-1 staining was primarily seen in stromal cells and weakly in mammary epithelial cells. Significantly higher levels of SDF-1 were seen in node-positive than in node-negative tumours (P = 0.05), in tumours that metastasized (P = 0.05), and tumours from patients who died (P = 0.03) than in tumours from patients who were disease free. It was most notable that levels of SDF-1 correlated significantly with overall survival (P = 0.001) and incidence-free survival (P = 0.035).

Conclusion

SDF-1 can increase the invasiveness and migration of breast cancer cells. Its levels correlated with node involvement and long-term survival in patients with breast cancer. SDF-1 may therefore have potential value in assessing clinical outcomes of patients with breast cancer.
Appendix
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Literature
1.
2.
Lacey JV, Devesa SS, Brinton LA: Recent trends in breast cancer incidence and mortality. Environ Mol Mutagen. 2002, 39: 82-88. 10.1002/em.10062.CrossRefPubMed
3.
Figueroa JA, Yee D, McGuire WL: Prognostic indicators in early breast cancer. Am J Med Sci. 1993, 305: 176-182.CrossRefPubMed
4.
Jatoi I, Hilsenbeck SG, Clark GM, Osborne CK: Significance of axillary lymph node metastasis in primary breast cancer. J Clin Oncol. 1999, 17: 2334-2340.PubMed
5.
Moore MAS: The role of chemoattraction in cancer metastases. BioEssays. 2001, 23: 674-676. 10.1002/bies.1095.CrossRefPubMed
6.
Phillips RJ, Burdick MD, Lutz M, Belperio JA, Keane MP, Strieter RM: The stromal derived factor-1/CXCL12-CXC chemokine receptor4 biological axis in non–small cell lung cancer metastases. Am J Respir Crit Care Med. 2003, 167: 1676-1686. 10.1164/rccm.200301-071OC.CrossRefPubMed
7.
Hart IR, Fidler IJ: Role of organ selectivity in the determination of metastatic patterns of B16 melanoma. Cancer Res. 1980, 40: 2281-2287.PubMed
8.
Nagasawa T, Kikutani H, Kishimoto T: Molecular cloning and structure of a pre-B-cell growth-stimulating factor. Proc Natl Acad Sci USA. 1994, 91: 2305-2309.CrossRefPubMedPubMedCentral
9.
Tashiro K, Tada H, Heilker R, Shirozu M, Nakano T, Honjo T: Signal sequence trap: a cloning strategy for secreted proteins and type I membrane proteins. Science. 1993, 261: 600-603.CrossRefPubMed
10.
Shirozu M, Nakano T, Inazawa J, Tashiro K, Tada H, Shinohara T, Honjo T: Structure and chromosomal localization of the human stromal cell-derived factor 1 (SDF1) gene. Genomics. 1995, 28: 495-500. 10.1006/geno.1995.1180.CrossRefPubMed
11.
Fernandis AZ, Prasad A, Band H, Klosel R, Ganju RK: Regulation of CXCR4 mediated chemotaxis and chemoinvasion of breast cancer cells. Oncogene. 2004, 23: 157-167. 10.1038/sj.onc.1206910.CrossRefPubMed
12.
Libura J, Drukala J, Majka M, Tomescu O, Navenot JM, Kucia M, Marquez L, Peiper SC, Barr FG, Janowska-Wieczorek A, Ratajczak MZ: CXCR4-SDF-1 signaling is active in rhabdomyosarcoma cells and regulates locomotion, chemotaxis, and adhesion. Blood. 2002, 100: 2597-2606. 10.1182/blood-2002-01-0031.CrossRefPubMed
13.
Zou YR, Kottmann AH, Kuroda M, Taniuchi I, Littman DR: Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature. 1998, 393: 595-599. 10.1038/31269.CrossRefPubMed
14.
Nagasawa UT, Tachibana UK, Kishimoto T: A novel CXC chemokine PBSF/SDF-1 and its receptor CXCR4: their functions in development, hematopoiesis and HIV infection. Semin Immunol. 1998, 10: 179-185. 10.1006/smim.1998.0128.CrossRefPubMed
15.
Tachibana K, Hirota S, Iizasa H, Yoshida H, Kawabata K, Kataoka Y, Kitamura Y, Matsushima K, Yoshida N, Nishikawa S, et al: The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract. Nature. 1998, 393: 591-594. 10.1038/31261.CrossRefPubMed
16.
Salcedo R, Wasserman K, Young HA, Grimm MC, Howard OM, Anver MR, Kleinman HK, Murphy WJ, Oppenheim JJ: Vascular endothelial growth factor and basic fibroblast growth factor induce expression of CXCR4 on human endothelial cells: in vivo neovascularization induced by stromal derived factor-1α. Am J Pathol. 1999, 154: 1125-1135.CrossRefPubMedPubMedCentral
17.
Yamaguchi J, Kusano KF, Masuo O, Kawamoto A, Silver M, Murasawa S, Bosch-Marce M, Masuda H, Losordo DW, Isner JM, et al: Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization. Circulation. 2003, 107: 1322-1328. 10.1161/01.CIR.0000055313.77510.22.CrossRefPubMed
18.
Geminder H, Sagi-Assif O, Goldberg L, Meshel T, Rechavi G, Witz IP, Ben-Baruch A: 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 Immunol. 2001, 167: 4747-4757.CrossRefPubMed
19.
Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, et al: Involvement of chemokine receptors in breast cancer metastasis. Nature. 2001, 410: 50-56. 10.1038/35065016.CrossRefPubMed
20.
Zeelenberg IS, Ruuls-Van Stalle L, Roos E: The chemokine receptor CXCR4 is required for outgrowth of colon carcinoma micrometastases. Cancer Res. 2003, 63: 3833-3839.PubMed
21.
Jiang WG, Hiscox S, Hallett MB, Horrobin DF, Mansel RE, Puntis MCA: Regulation of the expression of E-cadherin on human cancer cells by gamma linolenic acid. Cancer Res. 1995, 55: 5043-5048.PubMed
22.
Jiang WG, Hiscox S, Cai J, Martin T, Matsumoto K, Nakamura T, Mansel RE: Antagonistic effects of NK4, an novel HGF variant, on the in vitro angiogenesis of human vascular endothelial cells. Clin Cancer Res. 1999, 5: 3695-3703.PubMed
23.
Jiang WG, Watkins G, Fodstad O, Douglas-Jones A, Mokbel K, Mansel RE: Differential expression of the CCN family members Cyr61 from CTGF and Nov in human breast cancer. Endocr Relat Cancer. 2004, 11: 781-791. 10.1677/erc.1.00825.CrossRefPubMed
24.
King JAC, Ofori-Acquah AF, Stevens T, Al-Mehdi AB, Fodstad O, Jiang WG: Prognostic value of ALCAM in human breast cancer. Breast Cancer Res. 2004, 6: R478-R487. 10.1186/bcr815.CrossRefPubMedPubMedCentral
25.
Jiang WG, Douglas-Jones A, Mansel RE: Level of expression of PPAR-gamma and its co-activator (PPAR-GCA) in human breast cancer. Int J Cancer. 2003, 106: 752-757. 10.1002/ijc.11302.CrossRefPubMed
26.
Rossi D, Zlotnik A: The biology of chemokines and their receptors. Annu Rev Immunol. 2000, 18: 217-242. 10.1146/annurev.immunol.18.1.217.CrossRefPubMed
27.
Murdoch C: CXCR4: chemokine receptor extraordinaire. Immunol Rev. 2000, 177: 175-184. 10.1034/j.1600-065X.2000.17715.x.CrossRefPubMed
28.
Feng Y, Broder CC, Kennedy PE, Berger EA: HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science. 1996, 272: 872-877.CrossRefPubMed
29.
Yun HJ, Jo DY: Production of stromal cell-derived factor-1 (SDF-1) and expression of CXCR4 in human bone marrow endothelial cells. J Korean Med Sci. 2003, 18: 679-685.CrossRefPubMedPubMedCentral
30.
Aust G, Steinert M, Kiessling S, Kamprad M, Simchen C.: Reduced expression of stromal-derived factor 1 in autonomous thyroid adenomas and its regulation in thyroid-derived cells. J Clin Endocrinol Metab. 2001, 86: 3368-3376. 10.1210/jc.86.7.3368.PubMed
31.
Koshiba T, Hosotani R, Miyamoto Y, Ida J, Tsuji S, Nakajima S, Kawaguchi M, Kobayashi H, Doi R, Hori T, et al: Expression of stromal cell-derived factor 1 and CXCR4 ligand receptor system in pancreatic cancer: a possible role for tumor progression. Clin Cancer Res. 2000, 6: 3530-3535.PubMed
32.
Bartolome RA, Galvez BG, Longo N, Baleux F, Van Muijen GN, Sanchez-Mateos P, Arroyo AG, Teixido J: Stromal cell-derived factor-1 promotes melanoma cell invasion across basement membranes involving stimulation of membrane-type 1 matrix metalloproteinase and Rho GTPase activities. Cancer Res. 2004, 64: 2534-2543.CrossRefPubMed
33.
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. Mol Endocrinol. 2003, 17: 792-803. 10.1210/me.2002-0438.CrossRefPubMed
34.
Li YM, Pan Y, Wei Y, Cheng X, Zhou BP, Tan M, Zhou X, Xia W, Hortobagyi GN, Yu D, et al: Upregulation of CXCR4 is essential for HER2-mediated tumor metastasis. Cancer Cell. 2004, 6: 459-469. 10.1016/j.ccr.2004.09.027.CrossRefPubMed
35.
Imai K, Kobayashi M, Wang J, Shinobu N, Yoshida H, Hamada J, Shindo M, Higashino F, Tanaka J, Asaka M, et al: Selective secretion of chemoattractants for haemopoietic progenitor cells by bone marrow endothelial cells: a possible role in homing of haemopoietic progenitor cells to bone marrow. Br J Haematol. 1999, 106: 905-911. 10.1046/j.1365-2141.1999.01644.x.CrossRefPubMed
36.
Arai J, Yasukawa M, Yakushijin Y, Miyazaki T, Fujita S: Stromal cells in lymph nodes attract B-lymphoma cells via production of stromal cell-derived factor-1. Eur J Haematol. 2000, 64: 323-332. 10.1034/j.1600-0609.2000.90147.x.CrossRefPubMed
37.
Fedyk ER, Jones D, Critchley HO, Phipps RP, Blieden TM, Springer TA: Expression of stromal-derived factor-1 is decreased by IL-1 and TNF and in dermal wound healing. J Immunol. 2001, 166: 5749-5755.CrossRefPubMed
38.
Hall JM, Korach KS: Stromal cell-derived factor 1 (SDF-1), a novel target of estrogen receptor action, mediates the mitogenic effects of estradiol in ovarian and breast cancer cells. Mol Endocrinol. 2003, 17: 792-803. 10.1210/me.2002-0438.CrossRefPubMed
39.
Helbig G, Christopherson KW, Bhat-Nakshatri P, Kumar S, Kishimoto H, Miller KD, Broxmeyer HE, Nakshatri H: NF-κB promotes breast cancer cell migration and metastasis by inducing the expression of the chemokine receptor CXCR4. J Biol Chem. 2003, 278: 21631-21638. 10.1074/jbc.M300609200.CrossRefPubMed
40.
Bachelder RE, Wendt MA, Mercurio AM: Vascular endothelial growth factor promotes breast carcinoma invasion in an autocrine manner by regulating the chemokine receptor CXCR41. Cancer Res. 2002, 62: 7203-7206.PubMed
41.
Kang H, Mansel RE, Jiang WG: The role of stroma-derived factor 1 (SDF-1) in the migration and invasion of breast cancer cells. Int J Oncol. 2005
42.
Kang W, Watkins G, Douglas-Jones A, Mansel RE, Jiang WG: The elevated level of CXCR4 expression is correlated with lymph node metastasis in human breast cancer. Breast. 2005,
43.
Kato M, Kitayama J, Kazama S, Nagawa H: Expression pattern of CXC chemokine receptor-4 is correlated with lymph node metastasis in human invasive ductal carcinoma. Breast Cancer Res. 2003, 5: R144-R150. 10.1186/bcr627.CrossRefPubMedPubMedCentral
Metadata
Title
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
Authors
Hua Kang
Gareth Watkins
Christian Parr
Anthony Douglas-Jones
Robert E Mansel
Wen G Jiang
Publication date
01-08-2005
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 4/2005
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr1022

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