Activities, localizations, and roles of serine proteases and their inhibitors in human brain tumor progression

The plasminogen activation system consists of plasminogen activators and their inhibitors, serine proteases, and serpins. The proteases and inhibitors regulate a variety of processes in tissue morphogenesis, differentiation, cell migration, and cancer cell invasiveness and metastasis. One of the plasminogen activators, urokinase-type plasminogen activator (uPA), binds to a specific surface and provides a localized cell surface proteolytic activity required for the destruction of extracellular matrix, which is a vital step in tumor cell invasion. The proteolytic activity of uPA is modulated by its cell surface receptor, as well as by plasminogen activator inhibitor type-1 (PAI-1) and, to a lesser degree, by other inhibitors. The role of plasminogen activators and their inhibitors in cancer invasion can be demonstrated in the development and progression of malignant brain tumors. Our findings indicate that uPA and PAI-1 expression are dramatically upregulated in malignant brain tumors in parallel with the histological progression of the tumors. The results suggest that these molecules may contribute to tumor invasion in addition to their significant role in angiogenesis. An evaluation of the plasminogen activation system could add diagnostic and prognostic significance to the evaluation of individual patients.