ELEVATED LEVELS OF M(R) 92,000 TYPE-IV COLLAGENASE IN HUMAN BRAIN-TUMORS

Local invasive growth is one of the key features of primary malignant brain tumors accompanied by remodeling of the vasculature and destruct ion of normal brain tissue. Tissue invasiveness is an essential biolog ical function used by a tumor to overcome the various barriers to its progression. The expression of metalloproteases has been shown to play a critical role in the invasive process in a number of tumors; howeve r, their expression in human brain tumors has not been previously repo rted. In this study we showed metalloprotease activities at M(r) 240,0 00, 123,000, 92,000, 72,000, and 67,000 in brain tumor extracts. These enzyme activities were inhibited by EDTA, an inhibitor of metalloprot eases. Significant increases in levels of protease bands at M(r) 92,00 0, 123,000, and 240,000 were observed in glioblastoma and metastatic l ung tumors. Enzymatic inhibition and Western blotting with M(r) 92,000 type IV collagenase antibody confirmed the presence of M(r) 92,000 ty pe IV collagenase in all samples. Quantitative analysis by densitometr y showed 8-10-fold and 6-8-fold increases in M(r) 92,000 type IV colla genase activity in glioblastoma and metastatic lung carcinoma samples, respectively when compared with normal brain, meningioma, astrocytoma , metastatic colon, and breast carcinoma samples. These findings provi de evidence for elevated levels of metalloproteases in glioblastomas a nd suggest a therapeutic target for minimizing the invasive propensity of gliomas using protease inhibitors.