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PMID:11747814
| Citation |
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 and Noda, M (2001) The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis. Cell 107:789-800 |
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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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| Keywords |
Animals; Cells, Cultured; Down-Regulation; Embryo, Mammalian/cytology; Embryo, Mammalian/metabolism; Extracellular Matrix/physiology; GPI-Linked Proteins; Gene Targeting; Humans; Immunohistochemistry; Matrix Metalloproteinase 14; Matrix Metalloproteinase 2/antagonists & inhibitors; Matrix Metalloproteinase 2/genetics; Matrix Metalloproteinase 2/metabolism; Matrix Metalloproteinase 9/genetics; Matrix Metalloproteinase 9/metabolism; Matrix Metalloproteinases/genetics; Matrix Metalloproteinases/metabolism; Matrix Metalloproteinases, Membrane-Associated; Membrane Glycoproteins/genetics; Membrane Glycoproteins/metabolism; Metalloendopeptidases/antagonists & inhibitors; Metalloendopeptidases/genetics; Metalloendopeptidases/metabolism; Mice; Mice, Nude; Muscle, Smooth, Vascular/metabolism; Mutation; Neoplasm Transplantation; Neoplasms, Experimental/metabolism; Neoplasms, Experimental/pathology; Neovascularization, Pathologic; Neovascularization, Physiologic; Transfection; Tumor Cells, Cultured |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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