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

Am J Pathol. 1997 Oct;151(4):1105-13.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chloramphenicol O-Acetyltransferase / metabolism
  • Gelatinases / genetics
  • Gelatinases / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interleukin-8 / metabolism*
  • Interleukin-8 / pharmacology
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary*
  • Male
  • Matrix Metalloproteinase 2
  • Melanoma / metabolism
  • Melanoma / pathology
  • Melanoma / secondary*
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • RNA, Messenger / metabolism
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology*
  • Skin Neoplasms / secondary
  • Transfection
  • Tumor Cells, Cultured
  • Up-Regulation


  • Interleukin-8
  • RNA, Messenger
  • Chloramphenicol O-Acetyltransferase
  • Gelatinases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2