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Lebectin, a Macrovipera lebetina venom‐derived C‐type lectin, inhibits angiogenesis both in vitro and in vivo
Author(s) -
Pilorget Anthony,
Conesa Magali,
Sarray Sameh,
MichaudLevesque Jonathan,
Daoud Salma,
Kim Kwang Sik,
Demeule Michel,
Marvaldi Jacques,
El Ayeb Mohamed,
Marrakchi Naziha,
Béliveau Richard,
Luis José
Publication year - 2007
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20935
Subject(s) - in vivo , in vitro , lectin , venom , c type lectin , angiogenesis , chemistry , snake venom , disintegrin , microbiology and biotechnology , cancer research , biochemistry , biology , metalloproteinase , matrix metalloproteinase
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 αvβ3, αvβ5, and α5β1 integrins, as well as the α2, α3, α6, and β4 subunits. Our data show that lebectin acts as a very potent inhibitor (IC 50 ≈ 0.5 nM) of HBMEC adhesion and migration on fibronectin by blocking the adhesive functions of both the α5β1 and αV integrins. In addition, lebectin strongly inhibits both HBMEC in vitro tubulogenesis on Matrigel™ (IC 50 = 0.4 nM) and proliferation. Finally, using both a chicken CAM assay and a Matrigel™ 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. J. Cell. Physiol. 211: 307–315, 2007. © 2007 Wiley‐Liss, Inc.