Inhibition of VEGF-dependent angiogenesis by the anti-CD82 monoclonal antibody 4F9 through regulation of lipid raft microdomains

Biochem Biophys Res Commun. 2016 May 20;474(1):111-117. doi: 10.1016/j.bbrc.2016.04.081. Epub 2016 Apr 19.

Abstract

CD82 (also known as KAI1) belongs to the tetraspanin superfamily of type III transmembrane proteins, and is involved in regulating cell adhesion, migration and proliferation. In contrast to these well-established roles of CD82 in tumor biology, its function in endothelial cell (EC) activity and tumor angiogenesis is yet to be determined. In this study, we show that suppression of CD82 negatively regulates vascular endothelial growth factor (VEGF)-induced angiogenesis. Moreover, we demonstrate that the anti-CD82 mAb 4F9 effectively inhibits phosphorylation of VEGF receptor 2 (VEGFR2), which is the principal mediator of the VEGF-induced angiogenic signaling process in tumor angiogenesis, by regulating the organization of the lipid raft microdomain signaling platform in human EC. Our present work therefore suggests that CD82 on EC is a potential target for anti-angiogenic therapy in VEGFR2-dependent tumor angiogenesis.

Keywords: 4F9; Angiogenesis; CD82; VEGF; VGFR2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / immunology
  • Cells, Cultured
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Endothelial Cells / immunology*
  • Humans
  • Kangai-1 Protein / immunology*
  • Membrane Microdomains / drug effects
  • Membrane Microdomains / immunology*
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / immunology*
  • Vascular Endothelial Growth Factor A / immunology*

Substances

  • Antibodies, Monoclonal
  • CD82 protein, human
  • Kangai-1 Protein
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A