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The impact of the stromal cell-derived factor-1–3′A and E-selectin S128R polymorphisms on breast cancer

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Abstract

Breast cancer is prone to metastasis even in early stage disease. Stromal cell-derived factor-1 (SDF-1) is a chemokine that has been associated with the egress of cancer cells from the primary focus and homing to distant sites, while E-selectin has been implicated in their trans-endothelial migration. This study was performed to evaluate the association between SDF-1–3′A and E-selectin S128R—two polymorphisms associated with enhanced function—and the risk of breast cancer, as well as their influence on breast cancer outcome. A retrospective analysis was conducted on 261 patients and 480 healthy controls using PCR–RFLP. The frequencies for the wild-type (GG), GA and AA genotypes of SDF-1 were 43.7, 45.2, and 11.1 % in patients, and 51.5, 41.3, and 7.3 % in healthy controls, respectively, while the SDF-1–3′A allelic frequency was 33.7 % at patients and 27.9 % at controls. The SDF-1–3′A carrier group of patients and the A allele of SDF-1 were overrepresented among the breast cancer cases (p = 0.04 and 0.02, respectively). For the E-selectin S128R polymorphism, the frequencies for the wild-type (AA), AC and CC genotypes were 58.6, 38.3, and 3.1 % in patients and 63.8, 31.4, and 3.8 % in controls, respectively, while the C allelic frequency was 22.2 % for patients and 19.5 % for controls. The CC genotype was associated with poorer survival. Otherwise, no significant association was detected between examined genotypes and tumor characteristics. Overall, our findings support that the SDF-1–3′A confers increased susceptibility to breast cancer and that the E-selectin S128R CC genotype may be related to poorer prognosis. Investigation in bigger cohorts of patients is warranted.

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References

  1. Ferlay J, Shin H, Bray F, Forman D, Mathers C, Parkin D (2010) GLOBOCAN 2008, Cancer incidence and mortality worldwide: IARC CancerBase No. 10 [Internet]. International Agency for Research on Cancer, Lyon, France

  2. American Cancer Society (2010) Cancer Facts & Figures 2010. American Cancer Society, Atlanta

    Google Scholar 

  3. Polyak K (2007) Breast cancer: origins and evolution. J Clin Invest 117(11):3155–3163. doi:10.1172/JCI33295

    Article  PubMed  CAS  Google Scholar 

  4. Tang P, Skinner KA, Hicks DG (2009) Molecular classification of breast carcinomas by immunohistochemical analysis: are we ready? Diagn Mol Pathol 18(3):125–132. doi:10.1097/PDM.0b013e31818d107b

    Article  PubMed  CAS  Google Scholar 

  5. Gupta GP, Massague J (2006) Cancer metastasis: building a framework. Cell 127(4):679–695. doi:10.1016/j.cell.2006.11.001

    Article  PubMed  CAS  Google Scholar 

  6. Zlotnik A, Yoshie O (2000) Chemokines: a new classification system and their role in immunity. Immunity 12(2):121–127

    Article  PubMed  CAS  Google Scholar 

  7. Vagima Y, Lapid K, Kollet O, Goichberg P, Alon R, Lapidot T (2011) Pathways implicated in stem cell migration: the SDF-1/CXCR4 axis. Methods Mol Biol 750:277–289. doi:10.1007/978-1-61779-145-1_19

    Article  PubMed  CAS  Google Scholar 

  8. Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verastegui E, Zlotnik A (2001) Involvement of chemokine receptors in breast cancer metastasis. Nature 410(6824):50–56. doi:10.1038/35065016

    Article  PubMed  CAS  Google Scholar 

  9. Winkler C, Modi W, Smith MW, Nelson GW, Wu X, Carrington M, Dean M, Honjo T, Tashiro K, Yabe D, Buchbinder S, Vittinghoff E, Goedert JJ, O’Brien TR, Jacobson LP, Detels R, Donfield S, Willoughby A, Gomperts E, Vlahov D, Phair J, O’Brien SJ (1998) Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC). Science 279(5349):389–393

    Article  PubMed  CAS  Google Scholar 

  10. Theodoropoulos GE, Panoussopoulos GS, Michalopoulos NV, Zambirinis CP, Taka S, Stamopoulos P, Gazouli M, Zografos G (2010) Analysis of the stromal cell-derived factor 1–3′A gene polymorphism in pancreatic cancer. Mol Med Rep 3(4):693–698. doi:10.3892/mmr_00000319

    CAS  Google Scholar 

  11. Laubli H, Borsig L (2010) Selectins promote tumor metastasis. Semin Cancer Biol 20(3):169–177. doi:10.1016/j.semcancer.2010.04.005

    Article  PubMed  Google Scholar 

  12. Petruzzelli L, Takami M, Humes HD (1999) Structure and function of cell adhesion molecules. Am J Med 106(4):467–476

    Article  PubMed  CAS  Google Scholar 

  13. Somers WS, Tang J, Shaw GD, Camphausen RT (2000) Insights into the molecular basis of leukocyte tethering and rolling revealed by structures of P- and E-selectin bound to SLe(X) and PSGL-1. Cell 103(3):467–479

    Article  PubMed  CAS  Google Scholar 

  14. Sperandio M, Gleissner CA, Ley K (2009) Glycosylation in immune cell trafficking. Immunol Rev 230(1):97–113. doi:10.1111/j.1600-065X.2009.00795.x

    Article  PubMed  CAS  Google Scholar 

  15. Gout S, Morin C, Houle F, Huot J (2006) Death receptor-3, a new E-selectin counter-receptor that confers migration and survival advantages to colon carcinoma cells by triggering p38 and ERK MAPK activation. Cancer Res 66(18):9117–9124. doi:10.1158/0008-5472.CAN-05-4605

    Article  PubMed  CAS  Google Scholar 

  16. Wenzel K, Hanke R, Speer A (1994) Polymorphism in the human E-selectin gene detected by PCR-SSCP. Hum Genet 94(4):452–453

    Article  PubMed  CAS  Google Scholar 

  17. Revelle BM, Scott D, Beck PJ (1996) Single amino acid residues in the E- and P-selectin epidermal growth factor domains can determine carbohydrate binding specificity. J Biol Chem 271(27):16160–16170

    Article  PubMed  CAS  Google Scholar 

  18. Edge SB, American Joint Committee on Cancer (2010) AJCC cancer staging manual. 7th edn. Springer, New York

  19. Panoussopoulos GS, Theodoropoulos G, Michalopoulos NV, Gazouli M, Flessas J, Taka S, Stamopoulos P, Manouras A, Zografos GC (2010) Analysis of E-selectin S128R gene polymorphism in pancreatic cancer. J Surg Oncol 102(6):604–607. doi:10.1002/jso.21648

    Article  PubMed  Google Scholar 

  20. Biancone L, Araki M, Araki K, Vassalli P, Stamenkovic I (1996) Redirection of tumor metastasis by expression of E-selectin in vivo. J Exp Med 183(2):581–587

    Article  PubMed  CAS  Google Scholar 

  21. Kang H, Watkins G, Parr C, Douglas-Jones A, Mansel RE, Jiang WG (2005) 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. Breast Cancer Res 7(4):R402–R410. doi:10.1186/bcr1022

    Article  PubMed  CAS  Google Scholar 

  22. Orimo A, Gupta PB, Sgroi DC, Arenzana-Seisdedos F, Delaunay T, Naeem R, Carey VJ, Richardson AL, Weinberg RA (2005) Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 121(3):335–348. doi:10.1016/j.cell.2005.02.034

    Article  PubMed  CAS  Google Scholar 

  23. Cabioglu N, Summy J, Miller C, Parikh NU, Sahin AA, Tuzlali S, Pumiglia K, Gallick GE, Price JE (2005) CXCL-12/stromal cell-derived factor-1alpha transactivates HER2-neu in breast cancer cells by a novel pathway involving Src kinase activation. Cancer Res 65(15):6493–6497. doi:10.1158/0008-5472.CAN-04-1303

    Article  PubMed  CAS  Google Scholar 

  24. Zagzag D, Lukyanov Y, Lan L, Ali MA, Esencay M, Mendez O, Yee H, Voura EB, Newcomb EW (2006) Hypoxia-inducible factor 1 and VEGF upregulate CXCR4 in glioblastoma: implications for angiogenesis and glioma cell invasion. Lab Invest 86(12):1221–1232. doi:10.1038/labinvest.3700482

    Article  PubMed  CAS  Google Scholar 

  25. Schioppa T, Uranchimeg B, Saccani A, Biswas SK, Doni A, Rapisarda A, Bernasconi S, Saccani S, Nebuloni M, Vago L, Mantovani A, Melillo G, Sica A (2003) Regulation of the chemokine receptor CXCR4 by hypoxia. J Exp Med 198(9):1391–1402. doi:10.1084/jem.20030267

    Article  PubMed  CAS  Google Scholar 

  26. Balkwill F (2004) Cancer and the chemokine network. Nat Rev Cancer 4(7):540–550. doi:10.1038/nrc1388

    Article  PubMed  CAS  Google Scholar 

  27. Zafiropoulos A, Crikas N, Passam AM, Spandidos DA (2004) Significant involvement of CCR2-64I and CXCL12-3a in the development of sporadic breast cancer. J Med Genet 41(5):e59

    Article  PubMed  CAS  Google Scholar 

  28. Razmkhah M, Talei AR, Doroudchi M, Khalili-Azad T, Ghaderi A (2005) Stromal cell-derived factor-1 (SDF-1) alleles and susceptibility to breast carcinoma. Cancer Lett 225(2):261–266. doi:10.1016/j.canlet.2004.10.039

    Article  PubMed  CAS  Google Scholar 

  29. Hassan S, Baccarelli A, Salvucci O, Basik M (2008) Plasma stromal cell-derived factor-1: host derived marker predictive of distant metastasis in breast cancer. Clin Cancer Res 14(2):446–454. doi:10.1158/1078-0432.CCR-07-1189

    Article  PubMed  CAS  Google Scholar 

  30. Miles FL, Pruitt FL, van Golen KL, Cooper CR (2008) Stepping out of the flow: capillary extravasation in cancer metastasis. Clin Exp Metastasis 25(4):305–324. doi:10.1007/s10585-007-9098-2

    Article  PubMed  CAS  Google Scholar 

  31. Kufe DW (2009) Mucins in cancer: function, prognosis and therapy. Nat Rev Cancer 9(12):874–885. doi:10.1038/nrc2761

    Article  PubMed  CAS  Google Scholar 

  32. Renkonen J, Paavonen T, Renkonen R (1997) Endothelial and epithelial expression of sialyl Lewis(x) and sialyl Lewis(a) in lesions of breast carcinoma. Int J Cancer 74(3):296–300. doi:10.1002/(SICI)1097-0215(19970620)74:3<296:AID-IJC11>3.0.CO;2-A

    Article  PubMed  CAS  Google Scholar 

  33. Julien S, Ivetic A, Grigoriadis A, QiZe D, Burford B, Sproviero D, Picco G, Gillett C, Papp SL, Schaffer L, Tutt A, Taylor-Papadimitriou J, Pinder SE, Burchell JM (2011) Selectin ligand sialyl-Lewis × antigen drives metastasis of hormone-dependent breast cancers. Cancer Res 71(24):7683–7693. doi:10.1158/0008-5472.CAN-11-1139

    Article  PubMed  CAS  Google Scholar 

  34. Hebbar M, Adenis A, Revillion F, Duhamel A, Romano O, Truant S, Libersa C, Giraud C, Triboulet JP, Pruvot FR, Peyrat JP (2009) E-selectin gene S128R polymorphism is associated with poor prognosis in patients with stage II or III colorectal cancer. Eur J Cancer 45(10):1871–1876. doi:10.1016/j.ejca.2009.03.011

    Article  PubMed  CAS  Google Scholar 

  35. Naidu R, Har YC, Taib NA (2011) Polymorphic variant Ser128Arg of E-selectin is associated with breast cancer risk and high grade tumors. Onkologie 34(11):592–597. doi:10.1159/000334060

    Article  PubMed  CAS  Google Scholar 

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None declared.

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Author notes

  1. Constantinos P. Zambirinis

    Present address: S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, NY, 10016, USA

Authors and Affiliations

  1. First Propaedeutic Surgical Department, Hippocration University Hospital, 7 Semitelou Street, 11528, Athens, Greece

    Panagiota Kontogianni, Constantinos P. Zambirinis, George Theodoropoulos, Nikolaos V. Michalopoulos, John Flessas & George C. Zografos

  2. Departments of Biology, School of Medicine, University of Athens, Athens, Greece

    Maria Gazouli

  3. Departments of Physiology, School of Medicine, University of Athens, Athens, Greece

    Maria Liberi

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  1. Panagiota Kontogianni
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  2. Constantinos P. Zambirinis
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Correspondence to George Theodoropoulos.

Additional information

P. Kontogianni and Constantinos P. Zambirinis have contributed equally to this work.

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Kontogianni, P., Zambirinis, C.P., Theodoropoulos, G. et al. The impact of the stromal cell-derived factor-1–3′A and E-selectin S128R polymorphisms on breast cancer. Mol Biol Rep 40, 43–50 (2013). https://doi.org/10.1007/s11033-012-1989-x

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  • DOI: https://doi.org/10.1007/s11033-012-1989-x

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