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

Melanoma Res. 2007 Aug;17(4):205-13. doi: 10.1097/CMR.0b013e3282a660ad.

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)-beta receptor:Fc fusion protein that scavenges TGF-beta receptors. Finally, we demonstrated that MMP-1 directly generated active TGF-beta 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-beta in vivo.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Collagen Type I / chemistry
  • Epithelial Cells / cytology
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung / cytology
  • Matrix Metalloproteinase 1 / biosynthesis*
  • Matrix Metalloproteinase 1 / chemistry*
  • Melanoma / enzymology
  • Melanoma / metabolism
  • Mink
  • Models, Biological
  • Neoplasm Metastasis
  • Transfection
  • Transforming Growth Factor beta / metabolism*

Substances

  • Collagen Type I
  • Transforming Growth Factor beta
  • Matrix Metalloproteinase 1