Membrane-type matrix metalloproteinase 1 (MT1-MMP) in cancer

Membrane-type matrix metalloproteinase 1 (MT1-MMP) is a new member of the MMP family that is expressed on the cell surface. MT1-MMP is frequently expressed in a variety of tumors and is thought to be an activator of progelatinase A that degrades type TV collagen in the basement membrane. We expressed a recombinant MT1-MMP in E. coli. The latent proform of MT1-MMP was processed by furin, and its activity to activate progelatinase A was demonstrated. The activated MT1-MMP was specifically inhibited by TIMP-2 by forming an enzyme-inhibitor complex. Since TIMP-2 in the complex retains its capability to form a complex with progelatinase A through its hemopexin-like domain, a ternary complex was formed. The ability of MT1-MMP to form a complex with progelatinase A through TIMP-2 correlates well to the receptor function of cells that express MT1-MMP for progelatinase A. Thus, the expression of MT1-MMP in cancer cells explains why gelatinase A expressed by stromal fibroblasts localizes on tumor cells and is activated there.