Control of angiogenesis by inhibitor of phospholipase A2.
OBJECTIVE
To investigate the potential effects of angiogenic process by secretory phospholipase A2 (sPLA2) inhibitor-HyPE (linking N-derivatized phosphatidyl-ethanolamine to hyaluronic acid) on human bone marrow endothelial cell line (HBME-1).


METHODS
In order to examine the suppressing effects of HyPE on HBME-1 proliferation, migration, and capillary-like tube formation, HBME-1 were activated hy angiogenic factor, specifically by basic fibroblast growth factor (b-FGF), vascular endothelial growth factor (VEGF), and oncostatin M (OSM) (at a final concentration of 25, 20, and 2.5 ng/mL, respectively), then HBME-1 proliferation, migration, and tube formation were studied in the absence or presence of HyPE. HBME-1 tube formation was specially analyzed in fibrin gel.


RESULTS
HyPE effectively inhibited HBME-1 proliferation and migration as a dose-dependent manner, whatever HBME-1 were grown in the control culture medium or stimulated with b-FGF, VEGF, or OSM. In fibrin, the formations of HBME-1 derived tube-like structures were enhanced by all angiogenic factors, but these were strongly suppressed by HyPE.


CONCLUSIONS
The results support the involvement of sPLA2 in angiogenesis. It is proposed that sPLA2 inhibitor introduces a novel approach in the control of cancer development.
Chen
Wenming
W
Beijing Chaoyang Hospital, Capital University of Medical Sciences, Beijing 100020. wenming_chen@yahoo.com
Li
Lihong
L
Zhu
Jiazhi
J
Liu
Jinwei
J
Soria
Jeannette
J
Soria
Claudine
C
Yedgar
Saul
S
D001854:Bone Marrow Cells / Q000166:cytology; D002196:Capillaries / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology; D009389:Neovascularization, Pathologic / Q000473:pathology*; D053683:Oncostatin M; D010455:Peptides / Q000037:antagonists & inhibitors; D010714:Phosphatidylethanolamines / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; C508351:OSM protein, human; D010455:Peptides; D010714:Phosphatidylethanolamines; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D053683:Oncostatin M; D006820:Hyaluronic Acid; D010741:Phospholipases A; D054467:Phospholipases A2