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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
MVL-PLA2, a snake venom phospholipase A2, inhibits angiogenesis through an increase in microtubule dynamics and disorganization of focal adhesions
PLoS ONE, Volume 5, No. 4, Article e10124, Year 2010
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Description
Integrins are essential protagonists of the complex multi-step process of angiogenesis that has now become a major target for the development of anticancer therapies. We recently reported and characterized that MVL-PLA2, a novel phospholipase A2 from Macrovipera lebetina venom, exhibited anti-integrin activity. In this study, we show that MVL-PLA2 also displays potent anti-angiogenic properties. This phospholipase A2 inhibited adhesion and migration of human microvascularendothelial cells (HMEC-1) in a dose-dependent manner without being cytotoxic. Using MatrigelTM and chick chorioallantoic membrane assays, we demonstrated that MVL-PLA2, as well as its catalytically inactivated form, significantly inhibited angiogenesis both in vitro and in vivo. We have also found that the actin cytoskeleton and the distribution of αvβ3 integrin, a critical regulator of angiogenesis and a major component of focal adhesions, were disturbed after MVL-PLA2 treatment. In order to further investigate the mechanism of action of this protein on endothelial cells, we analyzed the dynamic instability behavior of microtubules in living endothelial cells. Interestingly, we showed that MVL-PLA2 significantly increased microtubule dynamicity in HMEC-1 cells by 40%. We propose that the enhancement of microtubule dynamics may explain the alterations in the formation of focal adhesions, leading to inhibition of cell adhesion and migration. © 2010 Bazaa et al.
Authors & Co-Authors
Bazaa, Amine
Tunisia, Tunis
Institut Pasteur de Tunis
Pasquier, E.
France, Marseille
Aix Marseille Université
Defilles, Céline
France, Marseille
Aix Marseille Université
Limam, Inès
Tunisia, Tunis
Institut Pasteur de Tunis
Kessentini-Zouari, Raoudha
Tunisia, Tunis
Institut Pasteur de Tunis
Kallech-Ziri, Olfa
Tunisia, Tunis
Institut Pasteur de Tunis
Battari, Assou El
France, Marseille
Aix Marseille Université
Braguer, Diane
France, Marseille
Aix Marseille Université
El-Ayeb, Mohamed E.
Tunisia, Tunis
Institut Pasteur de Tunis
Marrakchi, Naziha
Tunisia, Tunis
Institut Pasteur de Tunis
Tunisia, Tunis
Faculté de Médecine de Tunis
Luis, José
France, Marseille
Aix Marseille Université
Statistics
Citations: 52
Authors: 11
Affiliations: 3
Identifiers
Doi:
10.1371/journal.pone.0010124
e-ISSN:
19326203
Research Areas
Cancer