Carcinosarcoma-induced endothelial cells tube formation through KDR/Flk-1 is blocked by TNP-470

Cancer Lett. 2004 Jan 8;203(1):45-50. doi: 10.1016/j.canlet.2003.08.020.

Abstract

We evaluated the usefulness of TNP-470 as an anti-cancer agent on a human uterine carcinosarcoma cell line (FU-MMT-1). FU-MMT-1 induced human arterial endothelial cell (HAEC) tube formation on an in vitro co-cultured model of FU-MMT-1 and HAECs on a matrix gel, and was blocked by vascular endothelial growth factor (VEGF)-2 receptor (KDR/Flk-1) tyrosine kinase inhibitor. Lower concentration of TNP-470 inhibited the tube formation. Cell proliferation of FU-MMT-1 but not HAEC was inhibited by lower concentration of TNP-470. In addition, lower concentration of TNP-470 blocked VEGF production on FU-MMT-1. Our results suggest that TNP-470 directly inhibited FU-MMT-1 but not HAEC growth accompanied with the inhibition of VEGF production, subsequently induced anti-angiogenesis on HAEC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Carcinosarcoma / pathology*
  • Cell Division / drug effects
  • Cyclohexanes
  • Endothelium, Vascular / drug effects*
  • Female
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Neovascularization, Pathologic / prevention & control*
  • O-(Chloroacetylcarbamoyl)fumagillol
  • Sesquiterpenes / pharmacology*
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*

Substances

  • Angiogenesis Inhibitors
  • Cyclohexanes
  • Sesquiterpenes
  • Vascular Endothelial Growth Factor Receptor-2
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • O-(Chloroacetylcarbamoyl)fumagillol