Endothelial secreted factors suppress mitogen deprivation-induced autophagy and apoptosis in glioblastoma stem-like cells.

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 sur...

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Autores principales:	Eva Maria Galan-Moya, Lucas Treps, Lisa Oliver, Hervé Chneiweiss, François M Vallette, Nicolas Bidère, Julie Gavard
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ef9bc722afb3425baeea9a09f32839bc
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spelling	oai:doaj.org-article:ef9bc722afb3425baeea9a09f32839bc2021-11-18T08:25:39ZEndothelial secreted factors suppress mitogen deprivation-induced autophagy and apoptosis in glioblastoma stem-like cells.1932-620310.1371/journal.pone.0093505https://doaj.org/article/ef9bc722afb3425baeea9a09f32839bc2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24682219/?tool=EBIhttps://doaj.org/toc/1932-6203Rapidly 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.Eva Maria Galan-MoyaLucas TrepsLisa OliverHervé ChneiweissFrançois M ValletteNicolas BidèreJulie GavardJulie GavardPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 3, p e93505 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eva Maria Galan-Moya Lucas Treps Lisa Oliver Hervé Chneiweiss François M Vallette Nicolas Bidère Julie Gavard Julie Gavard Endothelial secreted factors suppress mitogen deprivation-induced autophagy and apoptosis in glioblastoma stem-like cells.
description	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.
format	article
author	Eva Maria Galan-Moya Lucas Treps Lisa Oliver Hervé Chneiweiss François M Vallette Nicolas Bidère Julie Gavard Julie Gavard
author_facet	Eva Maria Galan-Moya Lucas Treps Lisa Oliver Hervé Chneiweiss François M Vallette Nicolas Bidère Julie Gavard Julie Gavard
author_sort	Eva Maria Galan-Moya
title	Endothelial secreted factors suppress mitogen deprivation-induced autophagy and apoptosis in glioblastoma stem-like cells.
title_short	Endothelial secreted factors suppress mitogen deprivation-induced autophagy and apoptosis in glioblastoma stem-like cells.
title_full	Endothelial secreted factors suppress mitogen deprivation-induced autophagy and apoptosis in glioblastoma stem-like cells.
title_fullStr	Endothelial secreted factors suppress mitogen deprivation-induced autophagy and apoptosis in glioblastoma stem-like cells.
title_full_unstemmed	Endothelial secreted factors suppress mitogen deprivation-induced autophagy and apoptosis in glioblastoma stem-like cells.
title_sort	endothelial secreted factors suppress mitogen deprivation-induced autophagy and apoptosis in glioblastoma stem-like cells.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/ef9bc722afb3425baeea9a09f32839bc
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Endothelial secreted factors suppress mitogen deprivation-induced autophagy and apoptosis in glioblastoma stem-like cells.

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