PRODUCTION OF MATRIX METALLOPROTEINASES AND A METALLOPROTEINASE INHIBITOR BY SWARM RAT CHONDROSARCOMA

Chondrosarcoma was found to produce a heat-labile collagenase and a he at-stable collagenase inhibitor. Unlike its cartilage counterpart, the inhibitory activity in chondrosarcoma could only be detected after he at-treatment. Western blot analysis of chondrosarcoma-derived inhibito r showed that this inhibitor cross-reacted with a polyclonal antibody raised against purified cartilage-derived collagenase inhibitor (1) at a M.W. of about 33 kDa. In addition to the collagenase activity, whic h appears to be matrix metalloproteinase I (MMP-1), chondrosarcoma ext racts were shown to contain four active gelatinase species which migra te at a molecular weight consistent with that reported for MMP-2 (72 k Da gelatinase, Type IV gelatinase) (2) and three active enzyme species which migrate at a molecular weight consistent with that reported for MMP-9 (92 kDa gelatinase, Type IV gelatinase) (3,4). In contrast, nor mal cartilage contained only two active and one latent form of MMP-2 i n significantly lower amounts than in chondrosarcoma. In the case of M MP-9, the same three species were present in normal cartilage and in c hondrosarcoma, but in lower amounts in the normal tissue. These result s suggest that chondrosarcoma might develop in vivo because the inhere nt proteolytic balance between the protease(s) and its endogenous inhi bitor(s) is shifted in favor of the enzyme. (C) 1994 Academic Press, I nc.