Increased invasion of neuroglioma cells transfected with urokinase plasminogen activator receptor cDNA

The cell-surface urokinase plasminogen activator receptor (uPAR) plays a ke y role in regulating plasminogen cleavage during extracellular proteolysis. Our recent results demonstrated that uPAR expression is critical for the i nvasiveness of human gliomas and down regulation of uPAR caused by antisens e cDNA transfection inhibits the invasion of these stable antisense uPAR-tr ansfectant clones. To study the role of uPARs in glioma cell invasion, a hu man neuroglioma cell line (H4) that normally produces low numbers of uPARs was transfected with the expression vector containing full-length human uPA R cDNA. Stable transfectants were analyzed for uPAR mRNA expression, recept or number, in vitro invasion and secretion of uPA and MMP-2. The uPAR-overp roducing clones showed a 4-fold increase in uPAR mRNA transcription and sim ilar to 40% increase in receptor numbers. uPAR-overproducing clones also in vaded through matrigel to a significantly greater extent than did parent ce ll line and vector clones. However, the uPAR-overexpressing clones and pare nt cell lines showed similar uPA and MMP-2 activities. These results sugges t that the over-production of uPAR on the surface of neuroglioma cells enha nces the invasiveness.