Small interfering RNA-mediated CXCR1 or CXCR2 knock-down inhibits melanoma tumor growth and invasion

Seema Singh, Anguraj Sadanandam, Michelle L. Varney, Kalyan C. Nannuru, Rakesh K. Singh

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

CXCR1 and CXCR2 are receptors for CXCL-8 and are differentially expressed on melanoma and endothelial cells. In this study, we determined the functional role of these receptors in melanoma progression. We stably knock-down the expression of CXCR1 and/or CXCR2 in A375-SM (SM; high metastatic) human melanoma cells by short-hairpin RNA transfection. Cell proliferation, migration, invasion, ERK phosphorlyation and cytoskeletal re-arrangements were carried out in vitro. In vivo growth was evaluated using murine subcutaneous xenograft model. Our data demonstrate that knock-down of CXCR1 and/or CXCR2 expression, inhibited melanoma cell proliferation, survival, migration and invasive potential in vitro. Moreover, we also observed inhibition of ERK phosphorylation and cytoskeltal rearrangement in SM-shCXCR1, SM-shCXCR2 and SM-shCXCR1/2 cells. Furthermore, when SM-shCXCR1 or SM-shCXCR2 cells implanted in nude mice, tumor growth, proliferation and microvessel density was significantly inhibited as compared to SM-control cells. In addition, we observed a significant increase in melanoma cell apoptosis in SM-shCXCR1 and SM-shCXCR2 tumors compared to SM-control tumors. Together, these data demonstrate that CXCR1 and CXCR2 expression play a critical role in human melanoma tumor progression and, functional blockade of CXCR1 and CXCR2 could be potentially used for future therapeutic intervention in malignant melanoma.

Original languageEnglish (US)
Pages (from-to)328-336
Number of pages9
JournalInternational Journal of Cancer
Volume126
Issue number2
DOIs
StatePublished - Jan 15 2010

Keywords

  • CXCR1
  • CXCR2
  • Chemokines
  • Melanoma
  • Tumor growth

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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