Skip to main content

Strong expression of chemokine receptor CXCR4 by renal cell carcinoma cells correlates with metastasis

Clinical & Experimental Metastasis volume 26, Article number: 1049 (2009) Cite this article

Abstract

The chemokine receptor CXCR4 is involved in the metastasis of many cancers. Recent evidence suggests that CXCR4 may be also involved in the metastasis of renal cell carcinoma. We analyzed the expression of CXCR4 in primary carcinomas, metastatic tissues and normal tissues using immunohistochemistry. We further investigated the migration of renal carcinoma cells in response to stimulation by CXCL12 in vitro. We also studied the subcellular localization of CXCR4 in renal cell carcinoma cells in response to CXCL12 by confocal microscopy. We observed the highest percentage of CXCR4 expression in renal cell carcinoma metastases compared with that in renal cell carcinomas and normal renal tissues. We further found that CXCR4 was localized predominantly in the membrane in primary renal cell carcinomas and predominantly in the cytoplasm in renal cell carcinoma metastases. Moreover, we found that CXCR4 was translocated from the cytoplasmic membrane to the cytoplasm upon stimulation by its ligand CXCL12. Renal cell carcinoma metastasis was associated with higher expression of CXCR4 and interaction of CXCR4 and its ligand CXCL12 resulted in the internalization of CXCR4 from the cytoplasmic membrane. These findings implicate the CXCR4-CXCL12 axis in the metastasis of renal cell carcinoma.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2

References

  1. Landis SH et al (1999) Cancer statistics. CA Cancer J Clin 49(1):8–31

    Article  CAS  PubMed  Google Scholar 

  2. Jones J, Libermann TA (2007) Genomics of renal cell cancer: the biology behind and the therapy ahead. Clin Cancer Res 1(2 Pt 2):685s–692s

    Article  Google Scholar 

  3. Nicolson GL (1993) Paracrine and autocrine growth mechanisms in tumor metastasis to specific sites with particular emphasis on brain and lung metastasis. Cancer Metastasis Rev 12(3–4):325–343

    Article  CAS  PubMed  Google Scholar 

  4. Kucia M et al (2004) CXCR4-SDF-1 signalling, locomotion, chemotaxis and adhesion. J Mol Histol 35(3):233–245

    Article  CAS  PubMed  Google Scholar 

  5. Cohen HT, McGovern FJ (2005) Renal-cell carcinoma. N Engl J Med 353(23):2477–2490

    Article  CAS  PubMed  Google Scholar 

  6. Butcher EC et al (1999) Lymphocyte trafficking and regional immunity. Adv Immunol 72:209–253

    Article  CAS  PubMed  Google Scholar 

  7. Campbell JJ, Butcher EC (2000) Chemokines in tissue-specific and microenvironment-specific lymphocyte homing. Curr Opin Immunol 12(3):336–341

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  9. Muller A et al (2001) Involvement of chemokine receptors in breast cancer metastasis. Nature 410(6824):50–56

    Article  CAS  PubMed  Google Scholar 

  10. Jiang SH et al (2008) Alternate arrangement of PpL B3 domain and SpA D domain creates synergistic double-site binding to VH3 and Vkappa regions of fab. DNA Cell Biol 27(8):423–431

    Article  CAS  PubMed  Google Scholar 

  11. Brand S et al (2005) CXCR4 and CXCL12 are inversely expressed in colorectal cancer cells and modulate cancer cell migration, invasion and MMP-9 activation. Exp Cell Res 310(1):117–130

    Article  CAS  PubMed  Google Scholar 

  12. Struckmann K et al (2008) pVHL co-ordinately regulates CXCR4/CXCL12 and MMP2/MMP9 expression in human clear-cell renal cell carcinoma. J Pathol 214(4):464–471

    Article  CAS  PubMed  Google Scholar 

  13. Murphy PM (2001) Chemokines and the molecular basis of cancer metastasis. N Engl J Med 345(11):833–835

    Article  CAS  PubMed  Google Scholar 

  14. Begum NA et al (1999) Reduced expression of the CXCR4 receptor mRNA in hepatocellular carcinoma and lack of inducibility of its ligand alpha-chemokine hIRH/SDF1alpha/PBSF in vitro. Int J Oncol 14(5):927–934

    CAS  PubMed  Google Scholar 

  15. Sehgal A et al (1998) CXCR-4, a chemokine receptor, is overexpressed in and required for proliferation of glioblastoma tumor cells. J Surg Oncol 69(2):99–104

    Article  CAS  PubMed  Google Scholar 

  16. Rempel SA et al (2000) Identification and localization of the cytokine SDF1 and its receptor, CXC chemokine receptor 4, to regions of necrosis and angiogenesis in human glioblastoma. Clin Cancer Res 6(1):102–111

    CAS  PubMed  Google Scholar 

  17. Schrader AJ et al (2002) CXCR4/CXCL12 expression and signalling in kidney cancer. Br J Cancer 86(8):1250–1256

    Article  CAS  PubMed  Google Scholar 

  18. Signoret N et al (1998) Differential regulation of CXCR4 and CCR5 endocytosis. J Cell Sci 111(Pt 18):2819–2830

    CAS  PubMed  Google Scholar 

  19. Kraitchman DL et al (2005) Dynamic imaging of allogeneic mesenchymal stem cells trafficking to myocardial infarction. Circulation 112(10):1451–1461

    Article  PubMed  Google Scholar 

  20. Nagasawa T, Kikutani H, Kishimoto T (1994) Molecular cloning and structure of a pre-B-cell growth-stimulating factor. Proc Natl Acad Sci USA 91(6):2305–2309

    Article  CAS  PubMed  Google Scholar 

  21. Signoret N et al (1997) Phorbol esters and SDF-1 induce rapid endocytosis and down modulation of the chemokine receptor CXCR4. J Cell Biol 139(3):651–664

    Article  CAS  PubMed  Google Scholar 

  22. Spano JP et al (2004) Chemokine receptor CXCR4 and early-stage non-small cell lung cancer: pattern of expression and correlation with outcome. Ann Oncol 15(4):613–617

    Article  PubMed  Google Scholar 

  23. Pleass RJ et al (2001) Streptococcal IgA-binding proteins bind in the Calpha 2-Calpha 3 interdomain region and inhibit binding of IgA to human CD89. J Biol Chem 276(11):8197–8204

    Article  CAS  PubMed  Google Scholar 

  24. Haviv YS et al (2004) Transcriptional targeting in renal cancer cell lines via the human CXCR4 promoter. Mol Cancer Ther 3(6):687–691

    CAS  PubMed  Google Scholar 

  25. Schrader AJ et al (2002) CXCR4/CXCL12 expression and signalling in kidney cancer. Br J Cancer 86:1250–1256

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Affiliations

  1. Department of Urology, Changhai Hospital, Second Military Medical University, 174 Changhai Road, 200433, Shanghai, China

    Linhui Wang, Liang Wang, Bo Yang, Qing Yang & Yinghao Sun

  2. Institute of Genetics, Fudan University, Shanghai, China

    Shouyi Qiao & Yingming Wang

Authors
  1. Linhui Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Liang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bo Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qing Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shouyi Qiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yingming Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yinghao Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yinghao Sun.

Additional information

Linhui Wang and Liang Wang contributed equally to this work.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Wang, L., Wang, L., Yang, B. et al. Strong expression of chemokine receptor CXCR4 by renal cell carcinoma cells correlates with metastasis. Clin Exp Metastasis 26, 1049 (2009). https://doi.org/10.1007/s10585-009-9294-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10585-009-9294-3

Keywords

  • CXCR4
  • CXCL12
  • Metastasis
  • Primary renal cell carcinoma