Functional invadopodia formed in glioblastoma stem cells are important regulators of tumor angiogenesis
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Christos Petropoulos1,2,3, Pierre-Olivier Guichet1,2,3, Konstantin Masliantsev1,2,3, Michel Wager4 and Lucie Karayan-Tapon1,2,3
1INSERM U1084, Laboratoire de Neurosciences Expérimentales et Clinique, Poitiers, F-86073, France
2Université de Poitiers, Poitiers, F-86073, France
3CHU de Poitiers, Laboratoire de Cancérologie Biologique, Poitiers, F-86022, France
4CHU de Poitiers, Service de Neurochirurgie, Poitiers, F-86021, France
Christos Petropoulos, email: email@example.com
Lucie Karayan-Tapon, email: firstname.lastname@example.org
Keywords: glioblastoma; invadopodia; angiogenesis; CD44; LIMKs
Received: September 22, 2017 Accepted: March 22, 2018 Published: April 17, 2018
Glioblastoma (GBM) represents the most common and lethal brain tumor. High vascularization, necrosis and invasiveness are hallmarks of GBM aggressiveness with recent data suggesting the important role of glioblastoma stem cells (GSCs) in these processes. It is now well established that cancer cells employ specialized structures termed invadosomes to potentiate invasion. However, the role of these structures in GBM dissemination remains poorly investigated. In this study, we showed that GBM-isolated GSCs form invadopodia-like protrusions endowed with degradative action. Interestingly, their formation depends on extracellular matrix (ECM) sensing via the CD44 receptor. We also found that GSCs invasive migration occurring during tubes assembly is promoted through invadopodia-mediated-ECM remodeling and LIM kinases signaling. Moreover, our study demonstrates that GSCs are highly adaptable cells that are able not only to restore damaged endothelial-derived tubes but also to generate in cooperation with normal endothelial cells (ECs) intact vascular channels. Taken together, our data provide new insights in GBM microvasculature and suggest that GSCs targeting in combination with anti-VEGF therapy may block tumor progression.
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