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

被引:110
作者
Galan-Moya, Eva Maria [1 ,2 ,3 ]
Le Guelte, Armelle [1 ,2 ,3 ]
Fernandes, Evelyne Lima [1 ,2 ,3 ]
Thirant, Cecile [3 ,4 ]
Dwyer, Julie [1 ,2 ,3 ]
Bidere, Nicolas [5 ]
Couraud, Pierre-Olivier [1 ,2 ,3 ]
Scott, Mark G. H. [1 ,2 ,3 ]
Junier, Marie-Pierre [3 ,4 ]
Chneiweiss, Herve [3 ,4 ]
Gavard, Julie [1 ,2 ,3 ]
机构
[1] Inst Cochin, INSERM U1016, F-75014 Paris, France
[2] CNRS, UMR 8104, F-75014 Paris, France
[3] Univ Paris 05, F-75006 Paris, France
[4] INSERM UMR 894, F-75014 Paris, France
[5] INSERM U1014, F-94800 Villejuif, France
关键词
brain tumour; endothelial; mTOR; secretome; stem cell; TUMOR-INITIATING CELLS; PERIVASCULAR NICHE; MALIGNANT GLIOMA; SELF-RENEWAL; IN-VIVO; GROWTH; IDENTIFICATION; INHIBITION; PHENOTYPE; SURVIVAL;
D O I
10.1038/embor.2011.39
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
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.
引用
收藏
页码:470 / 476
页数:7
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