Carcinosarcoma-induced endothelial cells tube formation through KDR/Flk-1 is blocked by TNP-470.
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.
Miura
Shin-ichiro
S
Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-Ku, 814-0180 Fukuoka, Japan. miuras@cis.fukuoka-u.ac.jp
Emoto
Makoto
M
Matsuo
Yoshino
Y
Kawarabayashi
Tatsuhiko
T
Saku
Keijiro
K
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D002296:Carcinosarcoma / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D003510:Cyclohexanes; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D012717:Sesquiterpenes; D040301:Vascular Endothelial Growth Factor Receptor-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000077609:O-(Chloroacetylcarbamoyl)fumagillol