Membrane-type matrix metalloproteinases (MT-MMPs) in cell invasion.
Activated gelatinase A is reportedly associated with tumor spread. We identified a novel matrix metalloproteinase that localizes on the cell surface and mediate the activation of progelatinase A. Thus, this progelatinase A activator was named membrane-type matrix metalloproteinase (MT1-MMP). Following the first-discovery of MT1-MMP, two other MT-MMPs which can activate progelatinase A were identified (MT2- and MT3-MMP, respectively). Among these three MT-MMPs, MT1-MMP is most often overexpressed in malignant tumor tissues, including lung and stomach carcinomas that contain activated gelatinase A. This suggests that MT1-MMP is most closely associated with the activation of progelatinase A in these tumor tissues. The expression of MT1-MMP also induced binding of gelatinase A to the cell surface by functioning as a receptor. The cell surface localization of proteinases has advantages over pericellular proteolysis. MT1-MMP and its family may play a central role in the cell surface localization and activation of progelatinase A and via this mechanism, tumor cells use exogenous progelatinase A to mediate the proteolysis associated with invasion and metastasis.
Sato
H
H
Department of Molecular Virology and Oncology, Kanazawa University, Japan. vhsato@kenroku.ipc.kanazawa-u.ac.jp
Okada
Y
Y
Seiki
M
M
D002874:Chromosome Mapping; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D018093:Gelatinases / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D053513:Matrix Metalloproteinase 16; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000201:enzymology*; D014158:Transcription, Genetic / Q000235:genetics*
D004792:Enzyme Precursors; C507102:MMP16 protein, human; D018093:Gelatinases; D053513:Matrix Metalloproteinase 16; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; C069860:progelatinase