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Secreted factors from brain endothelial cells maintain glioblastoma stem-like cell expansion through the mTOR pathway.


ABSTRACT: Glioma stem-cells are associated with the brain vasculature. However, the way in which this vascular niche regulates stem-cell renewal and fate remains unclear. Here, we show that factors emanating from brain endothelial cells positively control the expansion of long-term glioblastoma stem-like cells. We find that both pharmacological inhibition of and RNA interference with the mammalian target of rapamycin (mTOR) pathway reduce their spheroid growth. Conversely, the endothelial secretome is sufficient to promote this mTOR-dependent survival. Thus, interfering with endothelial signals might present opportunities to identify treatments that selectively target malignant stem-cell niches.

SUBMITTER: Galan-Moya EM 

PROVIDER: S-EPMC3090013 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Secreted factors from brain endothelial cells maintain glioblastoma stem-like cell expansion through the mTOR pathway.

Galan-Moya Eva Maria EM   Le Guelte Armelle A   Lima Fernandes Evelyne E   Thirant Cécile C   Dwyer Julie J   Bidere Nicolas N   Couraud Pierre-Olivier PO   Scott Mark G H MG   Junier Marie-Pierre MP   Chneiweiss Hervé H   Gavard Julie J   Gavard Julie J  

EMBO reports 20110401 5


Glioma stem-cells are associated with the brain vasculature. However, the way in which this vascular niche regulates stem-cell renewal and fate remains unclear. Here, we show that factors emanating from brain endothelial cells positively control the expansion of long-term glioblastoma stem-like cells. We find that both pharmacological inhibition of and RNA interference with the mammalian target of rapamycin (mTOR) pathway reduce their spheroid growth. Conversely, the endothelial secretome is suf  ...[more]

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