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) is critical for tumor cell invasion, Here, me report that the disruption of this binding by an u-PAR antagonist ATF-HSA inhibits in vitro the motility of endothelial cells in a dose-dependent manner, This inhibition was also observed when the cells were first stimulated with potent angiogenic factors, including bFGF or VEGF, [H-3]thymidine incorporation assay demonstrated that ATF-HSA did not affect the cell proliferation, 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 during migration revealed for the first time that its effect is related to a decrease in cell deformability, These results suggest that u-PAR antagonist may be a new approach to control angiogenesis.