A novel monoclonal antibody targeting a novel epitope of VE-cadherin inhibits vasculogenic mimicry of lung cancer cells

Vascular endothelial cadherin (VE-cadherin) was first found in vascular endothelial cells to maintain normal vascular structures and regulate endothelial cell permeability by homology adhesion. New evidence indicates that certain invasive tumor cells also express VE-cadherin, which is involved in vasculogenic mimicry to provide a blood supply required for tumor growth and metastasis. EC1 and EC3 domains of VE-cadherin were reported to be important for intercellular homology adhesion. In the present study, a monoclonal antibody specific to the outer-membrane immunoglobulin-like domains of VE-cadherin was generated and the binding epitope was identified as peptide LDREVVPWYNLTVEA in the EC4 domain. This antibody inhibited proliferation and capillary-like structure formation of lung cancer Glc-82 cells in 3D Matrigel culture in vitro. This effect was mediated by the inhibition of AKT phosphorylation. Our results suggested that the EC4 domain participates in VE-cadherin clustering and the antibody targeting the EC4 domain of VE-cadherin may be a promising anti-vasculogenic mimicry agent for cancer treatment.