BLOCKAGE OF UROKINASE RECEPTOR REDUCES IN-VITRO THE MOTILITY AND THE DEFORMABILITY OF ENDOTHELIAL-CELLS

The binding of urokinase (u-PA) to its cell surface receptor (u-PBR) i s critical for tumor cell invasion, Here, me report that the disruptio n of this binding by an u-PAR antagonist ATF-HSA inhibits in vitro the motility of endothelial cells in a dose-dependent manner, This inhibi tion was also observed when the cells were first stimulated with poten t angiogenic factors, including bFGF or VEGF, [H-3]thymidine incorpora tion assay demonstrated that ATF-HSA did not affect the cell prolifera tion, ATF-HSA mas more potent than plasmin inhibitors, suggesting that it exerts its effects not solely by inhibiting the remodeling of the extracellular matrix, In fact, analysis of the cell shape change durin g migration revealed for the first time that its effect is related to a decrease in cell deformability, These results suggest that u-PAR ant agonist may be a new approach to control angiogenesis.