Effect of fucoidan on fibroblast growth factor-2-induced angiogenesis in vitro.
Fucoidans are sulfated polysaccharides extracted from brown marine algae. A purified fucoidan fraction exhibits the same venous antithrombotic activity as heparin in rabbits, but with a lower anticoagulant effect. Because of its heparin-like structure, we postulated that fucoidan might modulate heparin-binding angiogenic growth factor activity. We thus studied its effect, at antithrombotic concentrations, on fibroblast growth factor (FGF)-2-induced proliferation and differentiation of human umbilical vein endothelial cells. The fucoidan effect on endothelial cell differentiation was evaluated by studying the expression of surface proteins (i.e. integrin, adhesion molecule) known to be modulated by FGF-2 and involved in angiogenesis, and by quantifying closed areas delimited by vascular tubes formed on reconstituted basement membrane. Fucoidan had no modulatory effect on the mitogenic activity of FGF-2, but significantly increased tubular structure density induced by FGF-2. Fucoidan alone increased alpha(6) integrin subunit expression with only partially organized tubular structure. In the presence of FGF-2, fucoidan enhanced alpha(6), beta(1) and PECAM-1 and inhibited alpha(v)beta(3) integrin expression. Heparin had no effect in these systems. The most striking effect of fucoidan was observed on alpha(6) expression and tube formation was abolished by monoclonal anti-alpha(6) antibodies. Fucoidan plus FGF-2 effect on alpha(6) expression was markedly decreased by monoclonal anti-FGF-2 antibodies, indicating that fucoidan acts mainly via FGF-2. These results show that, at antithrombotic concentrations, contrary to heparin, fucoidan can enhance vascular tube formation induced by FGF-2 with a modulation of the expression of surface proteins (mainly alpha(6)) involved in angiogenesis.
Matou
Sabine
S
INSERM U428, Université Paris V, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75908 Paris Cédex 15, France.
Helley
Dominique
D
Chabut
Delphine
D
Bros
Andrée
A
Fischer
Anne-Marie
AM
D000925:Anticoagulants / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D006801:Humans; D039503:Integrin alpha6 / Q000032:analysis / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis / Q000187:drug effects; D011134:Polysaccharides / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology
D000925:Anticoagulants; D039503:Integrin alpha6; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011134:Polysaccharides; D016222:Fibroblast Growth Factor 2; C007789:fucoidan