Functional characterization of MT3-MMP in transfected MDCK cells: progelatinase A activation and tubulogenesis in 3-D collagen lattice

MT3-MMP, a membrane-anchored matrix metalloproteinase, has been proposed to participate in the remodeling of extracellular matrix either by direct pro teolysis or via activating other enzymes such as progelatinase A. To test t his hypothesis, we analyzed the effect of exogenously transfected MT3-MMP i n a tissue remodeling system: growth and tubulogenesis of Madin-Darby canin e kidney (MDCK) cells in collagen gels. Although the parental cells require MMP activities for both growth and tubulogenesis, over-expression of wild- type MT3-MMP, but not its catalytically inactive mutant, leads to further e nhancement of both processes, independent of its downstream substrate, prog elatinase A, Mechanistically, MT3-MMP accomplishes such an effect by displa ying on cell surfaces as active species, ready to activate progelatinase A or degrade ECM molecules. These data strongly suggest that MT3-MMP possesse s the potential to directly enhance the growth and invasiveness of cells in vivo, two critical processes for development and carcinogenesis.