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Therapeutic activation of macrophages and microglia to suppress brain tumor-initiating cells

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Author
Sarkar, Susobhan
Doring, Axinia
Zemp, Franz J
Silva, Claudia
Lun, Xueqing
Wang, Xiuling
Kelly, John
Hader, Walter
Hamilton, Mark
Mercier, Philippe
Dunn, Jeffery F.
Kinniburgh, Dave
van Rooijen, Nico
Robbins, Stephen
Forsyth, Peter
Cairncross, Gregory
Weiss, Samuel
Yong, V Wee
Accessioned
2017-03-30T22:28:17Z
Available
2017-03-30T22:28:17Z
Issued
2013-12-08
Subject
Cancer
Cancer in the nervous system
CNS cancer
microglia
Type
journal article
Metadata
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Abstract
Brain tumor initiating cells (BTICs) contribute to the genesis and recurrence of gliomas. We examined whether the microglia and macrophages that are abundant in gliomas alter BTIC growth. We found that microglia derived from non-glioma human subjects markedly mitigated the sphere-forming capacity of glioma patient–derived BTICs in culture by inducing the expression of genes that control cell cycle arrest and differentiation. This sphere-reducing effect was mimicked by macrophages, but not by neurons or astrocytes. Using a drug screen, we validated amphotericin B (AmpB) as an activator of monocytoid cells and found that AmpB enhanced the microglial reduction of BTIC spheres. In mice harboring intracranial mouse or patient-derived BTICs, daily systemic treatment with non-toxic doses of AmpB substantially prolonged life. Notably, microglia and monocytes cultured from glioma patients were inefficient at reducing the sphere-forming capacity of autologous BTICs, but this was rectified by AmpB. These results provide new insights into the treatment of gliomas.
Grantingagency
Alberta Innovates – Health Solutions/Alberta Cancer Foundation, Canadian Institutes of Health Research
Refereed
Yes
Corporate
University of Calgary
Department
Neuroscience
Faculty
Medicine
Institution
University of Calgary
Publisher
Nature Publishing Group
Doi
doi:10.1038/nn.3597
http://dx.doi.org/10.11575/PRISM/33538
Uri
http://hdl.handle.net/1880/51890
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