Downregulation of urokinase-type plasminogen activator receptor (uPAR) induces caspase-mediated cell death in human glioblastoma cells

Urokinase-type plasminogen activator receptors (uPARs) play an important ro le in tumor invasion by localizing degradative enzymes at the invasive zone . Our previous studies with human glioblastoma cell line SNB19 expressing A S-uPAR stable tranfectant lose their invasive properties when injected in v ivo. The aim of the present study is to investigate whether the inhibition of tumor formation is due to apoptosis. Apoptosis is a highly conserved cel l suicide program essential for development and tissue homeostasis of all m etazoan organisms. Key to the apoptotic program is a family of cystein prot eases termed caspases, which are important for execution of apoptosis by cl eavage of essential cellular proteins. We found loss of mitochondrial trans membrane potential, release of cytochrome C from mitochondria and subsequen t activation of Caspase-9 in SNB19 AS-uPAR cells compared to parental and v ector controls. Our results indicate that suppression of uPAR results in ap optosis and suggest that Caspase-9 dependent apoptosis plays an important r ole in SNB19 AS-uPAR-induced apoptosis.