Senescence from glioma stem cell differentiation promotes tumor growth

Biochemical and Biophysical Research Communications
Rie OuchiHiroyuki Seimiya

Abstract

Glioblastoma (GBM) is a lethal brain tumor composed of heterogeneous cellular populations including glioma stem cells (GSCs) and differentiated non-stem glioma cells (NSGCs). While GSCs are involved in tumor initiation and propagation, NSGCs' role remains elusive. Here, we demonstrate that NSGCs undergo senescence and secrete pro-angiogenic proteins, boosting the GSC-derived tumor formation in vivo. We used a GSC model that maintains stemness in neurospheres, but loses the stemness and differentiates into NSGCs upon serum stimulation. These NSGCs downregulated telomerase, shortened telomeres, and eventually became senescent. The senescent NSGCs released pro-angiogenic proteins, including vascular endothelial growth factors and senescence-associated interleukins, such as IL-6 and IL-8. Conditioned medium from senescent NSGCs promoted proliferation of brain microvascular endothelial cells, and mixed implantation of GSCs and senescent NSGCs into mice enhanced the tumorigenic potential of GSCs. The senescent NSGCs seem to be clinically relevant, because both clinical samples and xenografts of GBM contained tumor cells that expressed the senescence markers. Our data suggest that senescent NSGCs promote malignant progression of GBM i...Continue Reading

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Citations

Feb 5, 2016·Biochemical and Biophysical Research Communications·Daiki HasegawaHiroyuki Seimiya
Mar 10, 2016·Biochimica Et Biophysica Acta·Patrick M PerrigueJan Barciszewski
Nov 7, 2017·Neuro-oncology·Yeshavanth Kumar Banasavadi-SiddegowdaBalveen Kaur
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Dec 24, 2018·Nature Reviews. Cancer·Uri Ben-DavidTodd R Golub
Apr 5, 2018·Acta Neuropathologica·Floris P BarthelRoel G W Verhaak
Jul 1, 2021·Oncology Letters·Yuying WuXinhua Zhang

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