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 C-14-labelled collagen films. As previously shown for proMMP 2 activation, TIMP 1 was an ineffective inhibit or of the process of collagenolysis whereas TIMP 2 was efficient and comple tely prevented collagen degradation. In the presence of the calcium ionopho re, ionomycin, proteolytic processing of MT1 MMP was restricted and collage nolysis 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 I inhibition remained poor relative to that of TIMP 2, The study demonstrated that synergy betwee n two non-conventional collagenases effectively degrades insoluble pericell ular collagen, Due to the membrane localisation of MTI MMP, this could pote ntially occur in a highly localised manner. (C) 2001 Federation of European Biochemical Societies, Published by Elsevier Science B.V. All rights reser ved.