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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.

Original publication

DOI

10.1016/s0092-8674(01)00597-9

Type

Journal article

Journal

Cell

Publication Date

14/12/2001

Volume

107

Pages

789 - 800

Keywords

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