• Susobhan Sarkar, Axinia Döring, Franz J Zemp, Claudia Silva, Xueqing Lun, Xiuling Wang, John Kelly, Walter Hader, Mark Hamilton, Philippe Mercier, Jeff F Dunn, Dave Kinniburgh, Nico van Rooijen, Stephen Robbins, Peter Forsyth, Gregory Cairncross, Samuel Weiss, and V Wee Yong.
• 1] Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada. [2] Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
• Nat. Neurosci. 2014 Jan 1; 17 (1): 46-55.

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.

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