The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis. |
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Authors: | J Oh R Takahashi S Kondo A Mizoguchi E Adachi R M Sasahara S Nishimura Y Imamura H Kitayama D B Alexander C Ide T P Horan T Arakawa H Yoshida S Nishikawa Y Itoh M Seiki S Itohara C Takahashi M Noda |
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Institution: | Department of Molecular Oncology, Kyoto University Graduate School of Medicine, 606-8501, Kyoto, Japan. |
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Abstract: | 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. |
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