ORIGINAL ARTICLESExpression of collagenase-1 (MMP-1) promotes melanoma growth through the generation of active transforming growth factor-βIida, Joji; McCarthy, James B.Author Information Department of Laboratory Medicine and Pathology, University of Minnesota, Comprehensive Cancer Center, Minneapolis, USA Correspondence to Joji Iida, PhD, Box 609 Mayo, 421 Delaware Street S.E., Department of Laboratory Medicine and Pathology, University of Minnesota, Comprehensive Cancer Center, Minneapolis, MN 55455, USA Tel: +1 612 625 5453; fax: +1 612 625 1121; e-mail: [email protected] Received 12 January 2007 Accepted 22 May 2007 Melanoma Research: August 2007 - Volume 17 - Issue 4 - p 205-213 doi: 10.1097/CMR.0b013e3282a660ad Buy Metrics 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. © 2007 Lippincott Williams & Wilkins, Inc.