Membrane type 1 matrix metalloproteinase and gelatinase A synergistically degrade type 1 collagen in a cell model.
A fibrosarcoma cell line transfected with the matrix metalloproteinase MT1 MMP showed an enhanced ability to degrade 14C-labelled collagen films. As previously shown for proMMP 2 activation, TIMP 1 was an ineffective inhibitor of the process of collagenolysis whereas TIMP 2 was efficient and completely prevented collagen degradation. In the presence of the calcium ionophore, ionomycin, proteolytic processing of MT1 MMP was restricted and collagenolysis did not occur indicating that the 63 kDa form of the enzyme is not a functional collagenase. The collagenolytic activity of MT1 MMP was shown to be enhanced by the addition of proMMP 2, but TIMP 1 inhibition remained poor relative to that of TIMP 2. The study demonstrated that synergy between two non-conventional collagenases effectively degrades insoluble pericellular collagen. Due to the membrane localisation of MT1 MMP, this could potentially occur in a highly localised manner.
School of Biological Sciences, University of East Anglia, NR4 7TJ, Norwich, UK.
S J
SJ
Atkinson
M L
ML
Patterson
M J
MJ
Butler
G
G
Murphy
D003094:Collagen / Q000187:drug effects / Q000378:metabolism*; D004357:Drug Synergism; D004792:Enzyme Precursors / Q000378:metabolism / Q000494:pharmacology; D005354:Fibrosarcoma / Q000378:metabolism*; D018093:Gelatinases / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism* / Q000494:pharmacology; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008954:Models, Biological; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000494:pharmacology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
D004792:Enzyme Precursors; D007476:Ionophores; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D015759:Ionomycin; D003094:Collagen; D018093:Gelatinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; C069860:progelatinase; D020778:Matrix Metalloproteinase 2