The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis.
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.
Pubmed ID: 11747814 RIS Download
Animals | Cells, Cultured | Down-Regulation | Embryo, Mammalian | Extracellular Matrix | GPI-Linked Proteins | Gene Targeting | Humans | Immunohistochemistry | Matrix Metalloproteinase 14 | Matrix Metalloproteinase 2 | Matrix Metalloproteinase 9 | Matrix Metalloproteinase Inhibitors | Matrix Metalloproteinases | Matrix Metalloproteinases, Membrane-Associated | Membrane Glycoproteins | Metalloendopeptidases | Mice | Mice, Nude | Muscle, Smooth, Vascular | Mutation | Neoplasm Transplantation | Neoplasms, Experimental | Neovascularization, Pathologic | Neovascularization, Physiologic | Transfection | Tumor Cells, Cultured