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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Blotting, Western
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Brain / blood supply
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Brain / cytology*
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Endothelial Cells / metabolism*
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Flow Cytometry
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Furans / pharmacology
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Glioblastoma / physiopathology*
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Humans
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Microscopy, Fluorescence
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Pyridines / pharmacology
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Pyrimidines / pharmacology
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RNA Interference
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RNA, Small Interfering / genetics
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Signal Transduction / physiology*
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Sirolimus / pharmacology
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Stem Cells / metabolism*
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Stem Cells / physiology
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TOR Serine-Threonine Kinases / antagonists & inhibitors
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TOR Serine-Threonine Kinases / genetics
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TOR Serine-Threonine Kinases / metabolism*
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Transfection
Substances
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Furans
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PI103
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Pyridines
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Pyrimidines
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RNA, Small Interfering
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TOR Serine-Threonine Kinases
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Sirolimus