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

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dc.contributor.authorSarkar, Susobhan
dc.contributor.authorDoring, Axinia
dc.contributor.authorZemp, Franz J
dc.contributor.authorSilva, Claudia
dc.contributor.authorLun, Xueqing
dc.contributor.authorWang, Xiuling
dc.contributor.authorKelly, John
dc.contributor.authorHader, Walter
dc.contributor.authorHamilton, Mark
dc.contributor.authorMercier, Philippe
dc.contributor.authorDunn, Jeffery F.
dc.contributor.authorKinniburgh, Dave
dc.contributor.authorvan Rooijen, Nico
dc.contributor.authorRobbins, Stephen
dc.contributor.authorForsyth, Peter
dc.contributor.authorCairncross, Gregory
dc.contributor.authorWeiss, Samuel
dc.contributor.authorYong, V Wee
dc.date.accessioned2017-03-30T22:28:17Z
dc.date.available2017-03-30T22:28:17Z
dc.date.issued2013-12-08
dc.description.abstractBrain 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.en_US
dc.description.grantingagencyAlberta Innovates – Health Solutions/Alberta Cancer Foundation, Canadian Institutes of Health Researchen_US
dc.description.refereedYesen_US
dc.identifier.doidoi:10.1038/nn.3597
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/33538
dc.identifier.issn1097-6256
dc.identifier.urihttp://hdl.handle.net/1880/51890
dc.language.isoenen_US
dc.publisherNature Publishing Groupen_US
dc.publisher.corporateUniversity of Calgary
dc.publisher.departmentNeuroscienceen_US
dc.publisher.facultyMedicineen_US
dc.publisher.institutionUniversity of Calgaryen_US
dc.subjectCanceren_US
dc.subjectCancer in the nervous systemen_US
dc.subjectCNS canceren_US
dc.subjectmicrogliaen_US
dc.titleTherapeutic activation of macrophages and microglia to suppress brain tumor-initiating cellsen_US
dc.typejournal article
thesis.degree.disciplineRadiology / Physiology / Clinical Neurosciences
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