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

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.

• Authors: Shin-ichiro Miura, Makoto Emoto, Yoshino Matsuo, Tatsuhiko Kawarabayashi, Keijiro Saku
• Journal: Cancer letters (Cancer Lett) Vol. 203 Issue 1 Pg. 45-50 (Jan 08 2004) ISSN: 0304-3835 [Print] Ireland
• PMID: 14670616 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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)