MT-MMP, THE CELL-SURFACE ACTIVATOR OF PROMMP-2 (PRO-GELATINASE-A), ISEXPRESSED WITH ITS SUBSTRATE IN MOUSE-TISSUE DURING EMBRYOGENESIS

Matrix metalloproteinases (MMPs), which degrade the components of the extracellular matrix, are key enzymes involved in the tissue remodelin g of multicellular organisms, Since MMPs are secreted as inactive zymo gens (pro-MMPs), they have to be activated to function, We identified a membrane-type MMP (MT-MMP) that activated proMMP-2 (pro-gelatinase A = 72 kDa type IV pro-collagenase) and described its expression on the invasive tumor cell surface, In this study we further examined the ex pression and role of MT-MMP in the activation of proMMP-2 during mouse embryogenesis, Northern blotting demonstrated that MT-MMP expression was increased together with that of MMP-2 and its inhibitor gene, TIMP -2, in embryos depending upon the number of days after gestation, and decreased with maturation after birth. In situ hybridization and immun ohistochemistry localized MT-MMP mRNA and protein in the cells of ossi fying tissues where both MMP-2 and TIMP-2 were expressed, Activated MM P-2 was detected by gelatin zymography in the lysates prepared from th e micro dissected tissues that expressed the three genes, The activati on rate of proMMP-2 was proportional to the expression of MMP-2 and MT -MMP, These results indicated that proMMP-2 activation through its act ivator, MT-MMP, is a physiological system used by organisms to initiat e tissue remodeling on the cell surface.