INHIBITION OF UROKINASE SYNTHESIS AND CELL-SURFACE BINDING ALTERS THEMOTILE BEHAVIOR OF EMBRYONIC ENDOCARDIAL-DERIVED MESENCHYMAL CELLS IN-VITRO

The expression of the serine protease urokinase is elevated during the epithelial-mesenchymal transformation of the endocardium in the devel oping avian heart. Elevated urokinase expression is associated with th e migrating mesenchymal cells of the atrioventricular canal and bulbot runcus and not the myocardium. Treatment of isolated endocardial-deriv ed mesenchymal cells with phosphatidyinositol-specific phospholipase C released urokinase and its receptor from the cell surface and caused significant alterations in cell morphology and motility. Likewise inhi bition of urokinase synthesis by treatment of cells with antisense oli gonucleotides also inhibited the migration and motility of the endocar dial-derived cells. These results suggest an important role for this e nzyme in cell-matrix interactions and cell migration during developmen t.