Competition between plasminogen and procathepsin B as a probe to demonstrate the in vitro activation of procathepsin B by the tissue plasminogen activator

The tissue plasminogen activator (tPA) was found to activate in vitro the procathepsin B purified from malignant ascitic fluids, This activation was time and dose dependent, and was associated with the processing of procathepsin B. The present study shows that tPA is a fast activator of procathepsin B in a neutral pH range, such that generation of cathepsin B activity and processing of procathepsin B are achieved after a 5-min incubation time at 37 degrees C, pH 7.4, In contrast, competition between plasminogen and procathepsin B was observed for the activation and processing by tPA, From these findings, a plasminogen activator pathway for procathepsin B activation related to the plasminogen concentration may exist. In. vivo this pathway may be involved in a proteolytic cascade linked to invasion and metastasis. (C) 1996 Academic Press, Inc.