Research Papers:

Functional invadopodia formed in glioblastoma stem cells are important regulators of tumor angiogenesis

Christos Petropoulos _, Pierre-Olivier Guichet, Konstantin Masliantsev, Michel Wager and Lucie Karayan-Tapon

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Oncotarget. 2018; 9:20640-20657. https://doi.org/10.18632/oncotarget.25045

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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

Correspondence to:

Christos Petropoulos, email: [email protected]

Lucie Karayan-Tapon, email: [email protected]

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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