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

Abstract

Vascular endothelial cadherin (VE-cadherin) was first found in vascular endothelial cells to maintain normal vascularstructuresandregulateendothelialcellpermeabilityby 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.