Production of matrix metalloproteinases and a metalloproteinase inhibitor by swarm rat chondrosarcoma.
Chondrosarcoma was found to produce a heat-labile collagenase and a heat-stable collagenase inhibitor. Unlike its cartilage counterpart, the inhibitory activity in chondrosarcoma could only be detected after heat-treatment. Western blot analysis of chondrosarcoma-derived inhibitor 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, which appears to be matrix metalloproteinase I (MMP-1), chondrosarcoma extracts were shown to contain four active gelatinase species which migrate at a molecular weight consistent with that reported for MMP-2 (72 kDa 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, normal cartilage contained only two active and one latent form of MMP-2 in significantly lower amounts than in chondrosarcoma. In the case of MMP-9, the same three species were present in normal cartilage and in chondrosarcoma, but in lower amounts in the normal tissue. These results suggest that chondrosarcoma might develop in vivo because the inherent proteolytic balance between the protease(s) and its endogenous inhibitor(s) is shifted in favor of the enzyme.
Moses
M A
MA
Department of Surgery, Children's Hospital, Boston, Massachusetts.
Shing
Y
Y
D000818:Animals; D002813:Chondrosarcoma / Q000201:enzymology*; D017364:Collagenases / Q000378:metabolism*; D006358:Hot Temperature; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008970:Molecular Weight; D051381:Rats; D017207:Rats, Sprague-Dawley; D012513:Sarcoma, Experimental / Q000201:enzymology
D061965:Matrix Metalloproteinase Inhibitors; D017364:Collagenases; D008666:Metalloendopeptidases