Opposite effects of endostatin on different endothelial cells

Cancer Biol Ther. 2004 Nov;3(11):1162-6; discussion 1167-8. doi: 10.4161/cbt.3.11.1219. Epub 2004 Nov 9.

Abstract

Endostatin was described as an anti-angiogenic factor. Therefore endostatin looked to be a new way in anti-angiogenic treatment of cancer. Unfortunately, up to now no objective response were seen in clinical trials using endostatin. We compared two different endothelial cell types. Human umbilical vein endothelial cells (HUVEC) and endothelial cells derived from differentiated embryonic stem cells (eESC) were tested in view of endostatin induced proliferation, apoptosis, migration and endostatin binding. Both endothelial cell types had shown an opposite response to endostatin for all observed parameters in dependency of the used concentration. The quantity of HUVEC cells was slightly reduced to 84 +/- 8% by treating with 50 ng/ml endostatin whereas the eESC's showed a significant increase up to 142 +/- 12% under same conditions (p = 0.01). The observation that endostatin is able to evoke non-uniform response for proliferation, cell mount and migration of endothelial cells, with different endostatin binding characteristic, leads to the assumption that endostatin effect is strongly dependent from endothelial cell type. Furthermore the cell biological response at lower concentration on angiogenic eESC gives evidence for an angiogenic modulatory rather than a predicted anti-angiogenic role of endostatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / metabolism
  • Angiogenesis Inhibitors / pharmacology*
  • Apoptosis / drug effects*
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Endostatins / metabolism
  • Endostatins / pharmacology*
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects*
  • Humans
  • Neovascularization, Physiologic*
  • Stem Cells* / cytology
  • Stem Cells* / drug effects
  • Umbilical Veins / cytology
  • Umbilical Veins / drug effects

Substances

  • Angiogenesis Inhibitors
  • Endostatins