Vascular endothelial cadherin (VE-cadherin): Cloning and role in endothelial cell-cell adhesion

Objective: To identify proteins responsible for intercellular junction integrity in human umbilical vein endothelial cells (HUVEC). we produced a monoclonal antibody that recognized an endothelial cell-specific, junctionally restricted protein. We characterized and cloned the antigen to study its functional properties. Methods: The size and cellular distribution of the antigen were determined by immunofluorescence and immunoprecipitation. The molecule was cloned and transfected into cell lines, and its role in cell-cell adhesion and growth rate was determined. Results: Monoclonal antibody heel recognizes VE-cadherin, an endothelial cell-restricted cell adhesion molecule, VE-cadherin is localized to the borders between apposing endothelial cells but is diffusely distributed on subconfluent or migrating cells. Transfection of fibroblasts with VE-cadherin imparts to them the ability to adhere to each other in a calcium-dependent homophilic manner. Expression of VE-cadherin over a several-log range does not change the growth rate of these cells. Conclusions: Despite the fact that VE-cadherin is a "nonclassical" cadherin by structure. it functions as a classic cadherin by imparting to cells the ability to adhere in a calcium-dependent, homophilic manner. On HUVEC it appears to play a role in maintaining monolayer integrity.