Extracellular fragment of brain-specific angiogenesis inhibitor 1 suppresses endothelial cell proliferation by blocking alphavbeta5 integrin

Exp Cell Res. 2004 Mar 10;294(1):172-84. doi: 10.1016/j.yexcr.2003.11.008.


Brain-specific angiogenesis inhibitor 1 (BAI1) is a transmembrane protein with anti-angiogenic activity. The mechanisms underlying BAI1 activity are unknown. In this study, we found that overexpression of BAI1 increased cell death in human umbilical vein endothelial cells (HUVECs) and, to a lesser degree, in SHSY5Y and U343 cells. Conditioned medium from BAI1-transfected U343 cells inhibited proliferation of HUVECs, and this effect was neutralized by addition of anti-BAI1 serum. The conditioned medium contained four cleavage products of the BAI1 extracellular domain. BAI1's middle extracellular region containing five thrombospondin type 1 repeats (BAI1-TSR) was sufficient for BAI1's antiproliferative effect on HUVECs. BAI1's action on HUVECs was blocked by anti-alpha(v) integrin, but not by anti-CD36 antibody treatment. Introduction of alpha(v)beta(5) integrin into HEK293 cells rendered them susceptible to cell death by BAI1, and BAI1-TSR bound with alpha(v)beta(5) integrin, but not to alpha(v)beta(3) integrin in brain tissue. Fluorescent BAI1-TSR colocalized with alpha(v)beta(5) integrin in HUVECs. Together, our results indicate that BAI1 has antiproliferative action on surrounding endothelial cells by blocking alpha(v)beta(5) integrin, and its active region is BAI1-TSR. BAI1-TSR could be valuable for regulating brain angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / metabolism
  • Angiogenesis Inhibitors / pharmacology*
  • Angiogenic Proteins / chemistry
  • Angiogenic Proteins / metabolism
  • Angiogenic Proteins / pharmacology*
  • Apoptosis
  • Brain / metabolism
  • CD36 Antigens / immunology
  • Caspase Inhibitors
  • Cell Division / drug effects
  • Cell Line
  • Cells, Cultured
  • Culture Media, Conditioned
  • Cysteine Proteinase Inhibitors / pharmacology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Humans
  • Integrin alphaV / immunology
  • Integrins / analysis
  • Integrins / antagonists & inhibitors*
  • Integrins / physiology
  • Necrosis
  • Peptide Fragments / pharmacology
  • Receptors, G-Protein-Coupled
  • Receptors, Vitronectin / analysis
  • Receptors, Vitronectin / antagonists & inhibitors*
  • Receptors, Vitronectin / physiology


  • ADGRB1 protein, human
  • Angiogenesis Inhibitors
  • Angiogenic Proteins
  • CD36 Antigens
  • Caspase Inhibitors
  • Culture Media, Conditioned
  • Cysteine Proteinase Inhibitors
  • Integrin alphaV
  • Integrins
  • Peptide Fragments
  • Receptors, G-Protein-Coupled
  • Receptors, Vitronectin
  • integrin alphaVbeta5