Expression of CXCR1 and CXCR2 receptors in malignant melanoma with different metastatic potential and their role in interleukin-8 (CXCL-8) -mediated modulation of metastatic phenotype

Michelle L. Varney, Aihua Li, Bhavana J. Dave, Corazan D. Bucana, Sonny L. Johansson, Rakesh K. Singh

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

In the present study, we examined the autocrine/paracrine role of IL-8 in melanoma growth and metastasis by analyzing the expression and functional significance of IL-8 receptors, CXCR1 and CXCR2 in human malignant melanoma cells with different metastatic potential. CXCR1 and CXCR2 mRNA and protein levels were analyzed by reverse trannscriptase-based polymerase chain reaction, immunohistochemistry, immunoprecipitation, flow cytometry and ligand binding assay in melanoma cells in vitro and xenografted in nude mice. Melanoma cells constitutively expressed CXCR1 and CXCR2 mRNA and protein. Highly metastatic A375SM cells expressed higher levels of CXCR1 and CXCR2 mRNA and protein in vitro and in vivo as compared to low metastatic A375P and non-metastatic SBC-2 melanoma cells. Treatment of SBC-2 and A375P cells with exogenously added recombinant IL-8 significantly enhanced their proliferation and invasive potential. Further neutralizing antibodies to CXCR1 and CXCR2 inhibited proliferation and invasive potential of unstimulated and IL-8-stimulated A375P cells. In summary, the data suggest that constitutive expression of CXCR1 and CXCR2 play an important role regulating the IL-8-mediated metastatic phenotype in human malignant melanoma cells.

Original languageEnglish (US)
Pages (from-to)723-731
Number of pages9
JournalClinical and Experimental Metastasis
Volume20
Issue number8
DOIs
StatePublished - 2003

Keywords

  • Angiogenesis
  • CXCR1
  • CXCR2
  • Interleukin-8
  • Metastasis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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