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

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.

journal_name

Melanoma Res

journal_title

Melanoma research

authors

Iida J,McCarthy JB

doi

10.1097/CMR.0b013e3282a660ad

subject

Has Abstract

pub_date

2007-08-01 00:00:00

pages

205-13

issue

4

eissn

0960-8931

issn

1473-5636

pii

00008390-200708000-00001

journal_volume

17

pub_type

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