Journal
GLIA
Volume 59, Issue 3, Pages 472-485Publisher
WILEY
DOI: 10.1002/glia.21117
Keywords
glioma; mice; microglia; ablation; tuftsin; MIF/TKP-tuftsin fragment 1-3
Categories
Funding
- National Institutes of Health [R01NS42168, R01NS046006]
- DFG [SFB TRR43, Exc 25]
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Gliomas are highly aggressive and accompanied by numerous microglia/macrophages (MG/MP) in and about the tumor. Little is known about what MG/MP do in this setting, or whether modulating MG/MP activation might affect glioma progression. Here, we used a glioma-microglia in culture system to establish the effects the tumor and microglia have on each other. We assessed glioma progression in vivo after MG/MP ablation or in the setting of exaggerated MG/MP activation. We show that glioma cells activate microglia but inhibit their phagocytic activities. Local ablation of MG/MP in vivo decreased tumor size and improved survival curves. Conversely, pharmacological activation of MG/MP increased glioma size through stimulating tumor proliferation and inhibiting apoptosis. In agreement with recent reports, expression of the chemokine CCL21 is enhanced after MG/MP activation and correlates with tumor growth. Taken together, our findings demonstrate that inhibition of MG/MP activation may constitute a new and effective contribution towards suppressing glioma proliferation. (C)2010 Wiley-Liss, Inc.
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