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 language | English (US) |
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Pages (from-to) | 205-213 |
Number of pages | 9 |
Journal | Melanoma research |
Volume | 17 |
Issue number | 4 |
DOIs | |
State | Published - Aug 2007 |
Keywords
- Growth
- Invasion
- Matrix metalloproteinase
- Transforming growth factor