VE-cadherin cleavage by ovarian cancer microparticles induces β-catenin phosphorylation in endothelial cells
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Hamda Al Thawadi1,2, Nadine Abu-Kaoud2, Haleema Al Farsi1,2, Jessica Hoarau-Véchot2, Shahin Rafii3, Arash Rafii2,3, Jennifer Pasquier2,3
1Qatar Research Leadership Program, Qatar Foundation, Doha, Qatar
2Stem Cell and Microenvironment Laboratory, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar
3Department of Genetic Medicine, Weill Cornell Medical College, NY, USA
Jennifer Pasquier, e-mail: [email protected]
Keywords: microparticles, ovarian cancer, tumor microenvironment, β-catenin, angiogenesis
Received: August 19, 2015 Accepted: November 25, 2015 Published: December 19, 2015
Microparticles (MPs) are increasingly recognized as important mediators of cell-cell communication in tumour growth and metastasis by facilitating angiogenesis-related processes. While the effects of the MPs on recipient cells are usually well described in the literature, the leading process remains unclear. Here we isolated MPs from ovarian cancer cells and investigated their effect on endothelial cells. First, we demonstrated that ovarian cancer MPs trigger β-catenin activation in endothelial cells, inducing the upregulation of Wnt/β-catenin target genes and an increase of angiogenic properties. We showed that this MPs mediated activation of β-catenin in ECs was Wnt/Frizzled independent; but dependent on VE-cadherin localization disruption, αVβ3 integrin activation and MMP activity. Finally, we revealed that Rac1 and AKT were responsible for β-catenin phosphorylation and translocation to the nucleus. Overall, our results indicate that MPs released from cancer cells could play a major role in neo-angiogenesis through activation of beta catenin pathway in endothelial cells.
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