Lebectin, a Macrovipera lebetina venom-derived C-type lectin, inhibits angiogenesis both in vitro and in vivo.
Integrins play an essential role in endothelial cell motility processes during angiogenesis and thus present interesting targets for the development of new anti-angiogenic agents. Snake venoms naturally contain a variety of proteins that can affect integrin-ligand interactions. Recently, the C-type lectin proteins (CLPs) have been characterized as efficient modulators of integrin functions. In this study, we investigated the anti-angiogenic activity of lebectin, a newly discovered CLP from Macrovipera lebetina venom. Human brain microvascular endothelial cells (HBMEC), used as an in vitro model, express alphavbeta3, alphavbeta5, and alpha5beta1 integrins, as well as the alpha2, alpha3, alpha6, and beta4 subunits. Our data show that lebectin acts as a very potent inhibitor (IC(50) approximately 0.5 nM) of HBMEC adhesion and migration on fibronectin by blocking the adhesive functions of both the alpha5beta1 and alphaV integrins. In addition, lebectin strongly inhibits both HBMEC in vitro tubulogenesis on Matrigel trade mark (IC(50) = 0.4 nM) and proliferation. Finally, using both a chicken CAM assay and a Matrigel trade mark Plug assay in nude mice, our results show that lebectin displays potent anti-angiogenic activity in vivo. Lebectin thus represents a new C-type lectin with anti-angiogenic properties with great potential for the treatment of angiogenesis-related diseases.
Pilorget
Anthony
A
CNRS FRE 2737, Faculté de Pharmacie, bd Jean Moulin, Marseille, Cedex 5, France.
Conesa
Magali
M
Sarray
Sameh
S
Michaud-Levesque
Jonathan
J
Daoud
Salma
S
Kim
Kwang Sik
KS
Demeule
Michel
M
Marvaldi
Jacques
J
El Ayeb
Mohamed
M
Marrakchi
Naziha
N
Béliveau
Richard
R
Luis
José
J
D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001921:Brain / Q000098:blood supply; D002196:Capillaries / Q000166:cytology / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D003094:Collagen; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D046149:Embryo Culture Techniques; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005353:Fibronectins / Q000494:pharmacology; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors / Q000378:metabolism; D007797:Laminin; D037181:Lectins, C-Type / Q000302:isolation & purification / Q000502:physiology* / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000517:prevention & control*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011509:Proteoglycans; D040521:Subcutaneous Tissue / Q000098:blood supply; D013997:Time Factors; D014757:Viper Venoms / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D017819:Viperidae
D020533:Angiogenesis Inhibitors; D004338:Drug Combinations; D005353:Fibronectins; D016023:Integrins; D007797:Laminin; D037181:Lectins, C-Type; D011509:Proteoglycans; D014757:Viper Venoms; C478765:lebecetin protein, Macrovipera lebetina; C519594:lebectin protein, Macrovipera lebetina; C059485:matrigel; D003094:Collagen