A novel monoclonal antibody targeting a novel epitope of VE-cadherin inhibits vasculogenic mimicry of lung cancer cells
A novel monoclonal antibody targeting a novel epitope of VE-cadherin inhibits vasculogenic mimicry of lung cancer cells
复制标题
一种针对 VE-钙粘蛋白新表位的新型单克隆抗体抑制肺癌细胞的血管生成拟态
DOI：
10.3892/or.2018.6374
复制
发表时间：
2018-06-01
期刊：
影响因子：
4.2
通讯作者：
He, Yang
中科院分区：
文献类型：
--
作者：
Ding, Jie;Jia, Xi;He, Yang
血管内皮钙粘蛋白（Vascular endothelial cadherin，VE-cadherin）最早发现于血管内皮细胞，通过同源粘附来维持正常的血管结构和调节内皮细胞的通透性。新的证据表明，某些侵袭性肿瘤细胞也表达VE-钙粘蛋白，其参与血管生成拟态以提供肿瘤生长和转移所需的血液供应。VE-钙粘蛋白的EC 1和EC 3结构域被报道对细胞间同源粘附是重要的。在本研究中，特异性的VE-钙粘蛋白的外膜免疫球蛋白样结构域的单克隆抗体的产生和结合表位被确定为肽LDREVVPWYNLTVEA在EC 4结构域。该抗体在体外3D Matrigel培养中抑制肺癌Glc-82细胞的增殖和毛细血管样结构的形成。这种作用是通过抑制AKT磷酸化来介导的。我们的研究结果表明，EC 4结构域参与了VE-钙粘蛋白的聚集，靶向VE-钙粘蛋白的EC 4结构域的抗体可能是一个有前途的抗血管生成拟态剂用于癌症治疗。
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.