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| Item Type: | Article |
|---|---|
| Title: | Glioma stem cells but not bulk glioma cells upregulate IL-6 secretion in microglia/brain macrophages via toll-like receptor 4 signaling |
| Creators Name: | a Dzaye, O.D., Hu, F., Derkow, K., Haage, V., Euskirchen, P., Harms, C., Lehnardt, S., Synowitz, M., Wolf, S.A. and Kettenmann, H. |
| Abstract: | Peripheral macrophages and resident microglia constitute the dominant glioma-infiltrating cells. The tumor induces an immunosuppressive and tumor-supportive phenotype in these glioma-associated microglia/brain macrophages (GAMs). A subpopulation of glioma cells acts as glioma stem cells (GSCs). We explored the interaction between GSCs and GAMs. Using CD133 as a marker of stemness, we enriched for or deprived the mouse glioma cell line GL261 of GSCs by fluorescence-activated cell sorting (FACS). Over the same period of time, 100 CD133(+ )GSCs had the capacity to form a tumor of comparable size to the ones formed by 10,000 CD133(-)GL261 cells. In IL-6(-/-)mice, only tumors formed by CD133(+ )cells were smaller compared with wild type. After stimulation of primary cultured microglia with medium from CD133-enriched GL261 glioma cells, we observed an selective upregulation in microglial IL-6 secretion dependent on Toll-like receptor (TLR) 4. Our results show that GSCs, but not the bulk glioma cells, initiate microglial IL-6 secretion via TLR4 signaling and that IL-6 regulates glioma growth by supporting GSCs. Using human glioma tissue, we could confirm the finding that GAMs are the major source of IL-6 in the tumor context. |
| Keywords: | Glioma, Glioma-Associated Microglia/Brain Macrophages, Glioma Stem Cells, IL-6, Toll-Like Receptor 4, Animals, Chickens, Mice |
| Source: | Journal of Neuropathology and Experimental Neurology |
| ISSN: | 0022-3069 |
| Publisher: | Oxford University Press |
| Volume: | 75 |
| Number: | 5 |
| Page Range: | 429-440 |
| Date: | 1 May 2016 |
| Official Publication: | https://doi.org/10.1093/jnen/nlw016 |
| PubMed: | View item in PubMed |
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