Expression of interleukin-8 by human melanoma cells up-regulates MMP-2 activity and increases tumor growth and metastasis

Mario Luca, Suyun Huang, Jeffrey E. Gershenwald, Rakesh K. Singh, Reuven Reich, Menashe Bar-Eli

Research output: Contribution to journalArticle

347 Scopus citations

Abstract

Expression of interleukin-8 (IL-8) by human melanoma cells correlates with their metastatic potential. Moreover, UV-B irradiation of primary cutaneous melanoma cells induces IL-8 mRNA and protein production and increases both tumor growth and metastasis in nude mice. Although IL-8 has been shown to be an angiogenic factor, the biological consequences of increased IL-8 production by melanoma cells and the role of IL-8 in the metastatic process remains unclear. The purpose of this study was to determine the role of IL-8 in tumor growth and metastasis of human melanoma cells. Nonmetastatic SB-2 melanoma cells with negligible levels of IL-8 were transfected with IL-8 cDNA and subsequently analyzed for changes in their tumorigenic and metastatic potential. Enforced expression of IL-8 rendered the melanoma cells highly tumorigenic and increased their metastatic potential as compared with parental and control transfected cells. The IL-8- transfected cells displayed up-regulation in M(r) 72,000 collagenase type IV (MMP-2) mRNA and collagenase activity and increased invasiveness through Matrigel-coated filters. Moreover, when the MMP-2 promoter was linked upstream of the chloramphenicol acetyltransferase (CAT) reporter gene, CAT activity was up-regulated in IL-8 but not in control transfected cells, suggesting that IL-8 is involved in MMP-2 gene transcription. Activation of type IV collagenase by IL-8 can enhance the invasion of host stroma by the tumor cells and increase angiogenesis and, hence, metastasis.

Original languageEnglish (US)
Pages (from-to)1105-1113
Number of pages9
JournalAmerican Journal of Pathology
Volume151
Issue number4
StatePublished - Oct 1997

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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