Membrane-type matrix metalloproteinases (MT-MMPs) in tumor metastasis.
Activated gelatinase A is reportedly associated with tumor spread. We identified novel matrix metalloproteinases that localize on the cell surface and mediate the activation of progelatinase A. Thus, these progelatinase A activators were named membrane-type matrix metalloproteinase-1 and -2 (MT-MMP-1 and -2, respectively). MT-MMP-1 is overexpressed in malignant tumor tissues, including lung and stomach carcinomas that contain activated gelatinase A. This suggests that MT-MMP-1 is associated with the activation of progelatinase A in these tumor tissues. The expression of MT-MMP-1 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. MT-MMP-1 and its family may play a central role in the cell surface localization and activation of progelatinase A and via this mechanism, tumor cell use exogenous progelatinase A to mediate the proteolysis associated with invasion and metastasis.
Sato
H
H
Department of Molecular Virology and Oncology, Kanazawa University.
Seiki
M
M
D000595:Amino Acid Sequence; D000818:Animals; D017364:Collagenases / Q000737:chemistry / Q000378:metabolism*; D018093:Gelatinases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D020781:Matrix Metalloproteinase 1; D020778:Matrix Metalloproteinase 2; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D017386:Sequence Homology, Amino Acid
D008565:Membrane Proteins; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1