The role of intracellular proteases in brain tumor.

Abstract

Intracellular neutral and acid protease activities in normal brain and brain tumors were measured. As compared with normal brain tissue, the malignant glioma tissue showed 2-to 8-fold increase in specific activity of Ca2+-dependent neutral protease. We partially purified this protease from rat brain and found that it required Ca2+ absolutely and cysteine obligatorily for its activity. It converted an inactive pre-protein kinase M in the brain to an active protein kinase M. On the other hand, S-100 protein, a brain-specific acidic protein, inhibited this protease activity. These results suggest that the Ca2+dependent neutral protease, S-100 protein and protein kinase M may have a close relationship with one another. The Ca2+-dependent neutral protease was inhibited by leupeptin, an actinomycete protease inhibitor. Leupeptin was then found to inhibit very strongly the cell growth of G203 glioma in vitro, suggesting that leupeptin could be used for therapeutic purposes.