Adenovirus-mediated delivery of antisense gene to urokinase-type plasminogen activator receptor suppresses glioma invasion and tumor growth

The urokinase-type plasminogen activator (uPA) and uPA receptor (uPAR) play important roles in the proteolytic cascade involved in the invasiveness of gliomas and other invasive tumors. High-level expression of uPAR has been correlated with high-grade glioma cell lines and tumors. We report here tha t down-regulating uPAR levels by antisense strategy using an adenovirus con struct (Ad-uPAR) inhibited glioma invasion in Matrigel and spheroid in vitr o models, s,c, (U87-MG) and intracranial (SNB19) injections of Ad-uPAR-infe cted glioma cells did not produce tumors in nude mice. However, injection o f the Ad-uPAR construct into previously established s.c, U87-MG tumors in n ude mice caused regression of those tumors. Our results support the therape utic potential of targeting the uPA-uPAR system for the treatment of glioma s and other cancers.