EXPRESSION OF 72 KDA AND 92 KDA TYPE-IV COLLAGENASES FROM HUMAN GIANT-CELL TUMOR OF BONE

Basement membrane forms widespread barriers to tumor invasion, It has been shown that tumor-secreted, basement membrane-degrading enzymes, n amely metalloproteinases (MMPs) play an important role in tumor invasi on and metastasis. In this study,we determined the enzymatic activity, content, and mRNA of both the 72 kDa (MMP-2) and 92 kDa (MMP-9) MMPs in primary cultures of human giant-cell tumor of bone (GCT) in vitro a nd in tissue extracts (in vivo). Gelatin zymography showed the presenc e of lytic bands at M(r) 121000, 92000, and 72000, and these enzymatic activities were inhibited by EDTA, an inhibitor of MMPs. Western blot s with antibodies specific for MMP-2 and MMP-9 confirmed the presence of MMP-2 and MMP-9 both in vitro and in vivo, but GCT cells at late pa ssage showed only MMP-2. Northern blots using labeled cDNA probes spec ific for these molecules revealed the presence of 3.1 kb transcript fo r MMP-2 and a 2.9 kb transcript for MMP-9. Using specific antibodies t o 72 kDa and 92 kDa type IV collagenases, we studied their cellular di stribution by immunohistochemical means, Stronger immunoreactivity was found for 92 kDa type IV collagenase than 72 kDa type IV collagenase in the giant cells, It appears, therefore, that MMP-9 may play an impo rtant role in the malignant behavior of GCTs and suggests a potential therapeutic role for protease inhibitors in attempting to minimize the invasive behavior of GCTs.