INHIBITION OF CULTURED-CELL GROWTH BY VASCULAR ENDOTHELIAL CADHERIN (CADHERIN-5 VE-CADHERIN)

Endothelial cell proliferation is inhibited by the establishment of ce ll to cell contacts, Adhesive molecules at junctions could therefore p lay a role in transferring negative growth signals, The transmembrane protein VE-cadherin (vascular endothelial cadherin/cadherin-5) is sele ctively expressed at intercellular clefts in the endothelium. The intr acellular domain interacts with cytoplasmic proteins called catenins t hat transmit the adhesion signal and contribute to the anchorage of th e protein to the actin cytoskeleton, Transfection of VE-cadherin in bo th Chinese hamster ovary (CHO) and L929 cells confers inhibition of ce ll growth, Truncation of VE-cadherin cytoplasmic region, responsible f or linking catenins, does not affect VE-cadherin adhesive properties b ut abolishes its effect on cell growth, Seeding human umbilical vein e ndothelial cells or VE-cadherin transfectants on a recombinant VE-cadh erin amino-terminal fragment inhibited their proliferation, These data show that VE-cadherin homotypic engagement at junctions participates in density dependent inhibition Of cell growth, This effect requires b oth the extracellular adhesive domain and the intracellular catenin bi nding region of the molecule.