Protease inhibitor antipain suppresses 12-O-tetradecanoyl-phorbol-13-acetate induction of plasminogen activator in transformable mouse embryo fibroblasts.

Plasminogen activator (PA) activity was analyzed in normal and transformed 10T1/2 mouse fibroblasts treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and the protease inhibitors antipain, leupeptin, and soybean trypsin inhibitor (SBTI). TPA induced PA activity in normal 10T1/2 cells was inhibited by antipain. Transformed 10T1/2 cells maintained high levels of PA activity which were not further stimulated by the addition of TPA. Similarly, antipain inhibited the PA activity of the transformed cultures. Leupeptin and SBTI had no effect. These findings, in light of the fact that antipain has been shown to suppress the promotional effect of TPA in X-ray induced malignant transformation, may suggest a definite role for proteases in the transformational event or maintenance of the transformed state.