Endothelial Secreted Factors Suppress Mitogen Deprivation-Induced Autophagy and Apoptosis in Glioblastoma Stem-Like Cells

Abstract : Rapidly growing and highly vascularized tumors, such as glioblastoma multiforme, contain heterogeneous areas within the tumor mass, some of which are inefficiently supplied with nutrients and oxygen. While the cell death rate is elevated in such zones, tumor cells are still suspected to grow and survive independently of extracellular growth factors. In line with this, glioblastoma stem-like cells (GSCs) are found closely associated with brain vasculature in situ, and as such are most likely in a protected microenvironment. However, the behavior of GSCs under deprived conditions has not been explored in detail. Using a panel of 14 patient-derived GSCs, we report that ex vivo mitogen deprivation impaired self-renewal capability, abolished constitutive activation of the mTor pathway, and impinged on GSC survival via the engagement of autophagic and apoptotic cascades. Moreover, pharmacological inhibition of the mTor pathway recapitulated the mitogen deprivation scenario. In contrast, blocking either apoptosis or autophagy, or culturing GSCs with endothelial-secreted factors partly restored mTor pathway activation and rescued GSC survival. Overall, our data suggest that GSCs are addicted to mTor, as their survival and self-renewal are profoundly dependent on this signaling axis. Thus, as mTor governs the fate of GSCs under both deprivation conditions and in the presence of endothelial factors, it could be a key target for therapeutic purposes.
Type de document :
Article dans une revue
PLoS ONE, Public Library of Science, 2014, pp.e93505. 〈10.1371/journal.pone.0093505〉
Liste complète des métadonnées

Littérature citée [33 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-01075054
Contributeur : Mireille Bos <>
Soumis le : jeudi 16 octobre 2014 - 15:02:59
Dernière modification le : jeudi 11 janvier 2018 - 06:25:43
Document(s) archivé(s) le : samedi 17 janvier 2015 - 10:45:22

Fichier

journal.pone.0093505.pdf
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Collections

Citation

Eva Maria Galan-Moya, Lucas Treps, Lisa Oliver, Hervé Chneiweiss, François Vallette, et al.. Endothelial Secreted Factors Suppress Mitogen Deprivation-Induced Autophagy and Apoptosis in Glioblastoma Stem-Like Cells. PLoS ONE, Public Library of Science, 2014, pp.e93505. 〈10.1371/journal.pone.0093505〉. 〈inserm-01075054〉

Partager

Métriques

Consultations de la notice

238

Téléchargements de fichiers

80