Lebectin, a Macrovipera lebetina venom-derived C-type lectin, inhibits angiogenesis both in vitro and in vivo

Anthony Pilorget, Magali Conesa, Sameh Sarray, Jonathan Michaud-Levesque, Salma Daoud, Kwang Sik Kim, Michel Demeule, Jacques Marvaldi, Mohamed El Ayeb, Naziha Marrakchi, Richard Béliveau, José Luis

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

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 (IC50 ≈ 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™ (IC50 = 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.

Original languageEnglish (US)
Pages (from-to)307-315
Number of pages9
JournalJournal of Cellular Physiology
Volume211
Issue number2
DOIs
StatePublished - May 2007
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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