Modulation of CXCL-8 expression in human melanoma cells regulates tumor growth, angiogenesis, invasion, and metastasis

Sheng Wu, Seema Singh, Michelle L. Varney, Scott Kindle, Rakesh K. Singh

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

CXCL-8, a chemokine secreted by melanoma and stromal cells, serves as a growth and angiogenic factor for melanoma progression. This study evaluated how modulation of CXCL-8 levels in melanoma cell lines with different tumorigenic and metastatic potentials affected multiple tumor phenotypes. A375P cells (CXCL-8 low expressor) were stably transfected with a CXCL-8 mammalian expression vector to overexpress CXCL-8, whereas A375SM cells (CXCL-8 high expressor) were transfected with a CXCL-8 antisense expression vector to suppress CXCL-8 expression. Subsequent cell proliferation, migration, invasion, and soft-agar colony formation were analyzed, and in vivo tumor growth and metastasis were evaluated using mouse xenograft models. Our data demonstrate that overexpression of CXCL-8 significantly enhanced primary tumor growth and lung metastasis, accompanied by increased microvessel density in vivo, as compared with vector control-transfected cells. We also observed increased clonogenic ability, growth, and invasive potential of CXCL-8 overexpressing cells in vitro. Knockdown of CXCL-8 using an antisense vector resulted in increased cell death and reduced tumor growth relative to control. Taken together, these data confirm that CXCL-8 expression plays a critical role in regulating multiple cellular phenotypes associated with melanoma growth and metastasis.

Original languageEnglish (US)
Pages (from-to)306-317
Number of pages12
JournalCancer Medicine
Volume1
Issue number3
DOIs
StatePublished - Dec 2012

Keywords

  • Angiogenesis
  • CXCL-8
  • Melanoma
  • Metastasis
  • Proliferation

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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