EXPRESSION AND LOCALIZATION OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR IN HUMAN ASTROCYTOMAS IN-VIVO

Plasminogen activators regulate a variety of processes involved in tis sue morphogenesis, as well as cell differentiation, migration, and inv asion. We examined the relative amounts of mRNA and protein and locali zation of urokinase-type plasminogen activator (uPA) in human astrocyt omas in vivo. Using fibrin zymography and densitometric quantitation, we found that uPA activity was significantly higher in malignant astro cytomas, especially in glioblastomas, than it was in normal brain tiss ues or low-grade gliomas. The amounts of uPA mRNA, as determined by No rthern blot analysis, were higher in anaplastic astrocytomas and gliob lastomas than in normal brain tissues and low-grade gliomas, consisten t with the amounts of uPA activity. To investigate the cellular source of uPA in various tissues, we performed immunocytochemical localizati on of uPA protein and in situ hybridization of uPA mRNA with astrocyto mas and normal brain tissues. Immunocytochemical staining for uPA show ed strong immunoreactivity in the tumor cells and vasculature of gliob lastomas and anaplastic astrocytomas but undetectable or very low immu noreactivity for uPA in low-grade gliomas and normal brain tissues. uP A mRNA was located in astrocytoma and endothelial cells and was hetero geneously distributed within glioblastoma, with preferential localizat ion near vascular proliferation and at the leading edge of the tumor. uPA expression was dramatically higher in highly malignant astrocytoma s, especially glioblastomas, and was correlated with malignant progres sion of astrocytomas.