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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




Journal article



Publication Date





789 - 800


Department of Molecular Oncology, Kyoto University Graduate School of Medicine, 606-8501, Kyoto, Japan.


Muscle, Smooth, Vascular, Cells, Cultured, Tumor Cells, Cultured, Extracellular Matrix, Animals, Humans, Mice, Mice, Nude, Neoplasms, Experimental, Neovascularization, Pathologic, Metalloendopeptidases, Matrix Metalloproteinases, Membrane Glycoproteins, Immunohistochemistry, Gene Targeting, Transfection, Neoplasm Transplantation, Down-Regulation, Neovascularization, Physiologic, Mutation, Matrix Metalloproteinases, Membrane-Associated, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, Matrix Metalloproteinase 14, Embryo, Mammalian, GPI-Linked Proteins