Expression of collagenase-1 (MMP-1) promotes melanoma growth through the generation of active transforming growth factor-β

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Abstract

Tumor cell invasion through basement membranes and into stromal tissue are key steps for promoting growth and metastasis. Tumor cells express various extracellular-matrix-degrading enzymes such as matrix metalloproteinases (MMPs) to degrade extracellular matrix components to facilitate tumor migration and invasion. Histological and clinical studies suggest a role for MMP-1 (collagenase-1) in malignant melanoma invasion. In this study, we evaluated MMP-1 in regulating malignant phenotypes of human melanoma cells by generating human melanoma cells stably transfected with pro-MMP-1 cDNA. The transfectants expressed the active form of MMP-1 associated with cells and showed enhanced invasive and growth abilities in type I collagen gel. Furthermore, MMP-1 expression promoted anchorage-independent growth, which was inhibited in the presence of type II transforming growth factor (TGF)-β receptor:Fc fusion protein that scavenges TGF-β receptors. Finally, we demonstrated that MMP-1 directly generated active TGF-β from its latent form. Thus, these results suggest that MMP-1 produced from melanoma cells would play a role in tumor progression by both degrading matrix proteins and generating active growth factors such as TGF-β in vivo.

Original languageEnglish (US)
Pages (from-to)205-213
Number of pages9
JournalMelanoma research
Volume17
Issue number4
DOIs
StatePublished - Aug 2007

Keywords

  • Growth
  • Invasion
  • Matrix metalloproteinase
  • Transforming growth factor

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