Single chain Fv antibody against angiopoietin-2 inhibits VEGF-induced endothelial cell proliferation and migration in vitro

Biochem Biophys Res Commun. 2003 Oct 3;309(4):946-51. doi: 10.1016/j.bbrc.2003.08.086.

Abstract

Angiopoietin-2 (Ang2) promotes tumor growth and metastasis by specifically priming endothelial cells for angiogenesis. Multiple angiogenic factors up-regulate expression of Ang2, suggesting that Ang2 may be the common pathway in growth factor initiated-angiogenesis. Using phage display technology, we generated single chain Fv molecule against human Ang2 (scFv-Ang2) with high affinity (K(d)=0.01 microM) from a mouse phage antibody library. Compared with control scFv, the mouse scFv-Ang2 completely inhibited the proliferation of human umbilical vein endothelial cells (HUVECs) treated with vascular endothelial growth factor (VEGF, 10 ng/ml), but not that of the cells treated with either basic fibroblast growth factor, or angiotensin II, or Ang2. Chemotaxis assay showed that scFv-Ang2 could block completely Ang2-induced (100%) and partially VEGF-induced (49%) migration of HUVECs. The results indicate that Ang2 takes part in the VEGF-induced angiogenesis and scFv-Ang2 might be a promising compound in blocking both VEGF and Ang2 induced angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietin-2 / immunology*
  • Animals
  • Chemotaxis / drug effects*
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Female
  • Immunoglobulin Fragments / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / pharmacology

Substances

  • Angiopoietin-2
  • Immunoglobulin Fragments
  • Vascular Endothelial Growth Factor A