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

Ding,Jie; Jia,Xi; Zuo,Bin; He,Jun; Yang,Jianfeng; He,Yang

doi:10.3892/or.2018.6374

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

Authors:
- Jie Ding
- Xi Jia
- Bin Zuo
- Jun He
- Jianfeng Yang
- Yang He
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Affiliations: Ministry of Health Key Laboratory of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Cyrus Tang Hematology Center and Ministry of Education Engineering Center of Hematological Disease, and the Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu 215123, P.R. China, Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
Published online on: April 16, 2018 https://doi.org/10.3892/or.2018.6374
Pages: 2837-2844

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Abstract

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.

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