The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis.
Oh J., Takahashi R., Kondo S., Mizoguchi A., Adachi E., Sasahara RM., Nishimura S., Imamura Y., Kitayama H., Alexander DB., Ide C., Horan TP., Arakawa T., Yoshida H., Nishikawa S., Itoh Y., Seiki M., Itohara S., Takahashi C., Noda M.
Matrix metalloproteinases (MMPs) are essential for proper extracellular matrix remodeling. We previously found that a membrane-anchored glycoprotein, RECK, negatively regulates MMP-9 and inhibits tumor invasion and metastasis. Here we show that RECK regulates two other MMPs, MMP-2 and MT1-MMP, known to be involved in cancer progression, that mice lacking a functional RECK gene die around E10.5 with defects in collagen fibrils, the basal lamina, and vascular development, and that this phenotype is partially suppressed by MMP-2 null mutation. Also, vascular sprouting is dramatically suppressed in tumors derived from RECK-expressing fibrosarcoma cells grown in nude mice. These results support a role for RECK in the regulation of MMP-2 in vivo and implicate RECK downregulation in tumor angiogenesis.