gms | German Medical Science

65. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

11. - 14. Mai 2014, Dresden

Artikel

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Glioma-initiating cell-induced Interleukin-6 production is mediated by Toll-like receptor 4 in microglia

Meeting Abstract

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  • Omar Dildar a Dzaye - FG Zelluläre Neurowissenschaften, Max Delbrück Centrum Berlin-Buch, Berlin
  • Feng Hu - FG Zelluläre Neurowissenschaften, Max Delbrück Centrum Berlin-Buch, Berlin
  • Katja Derkow - Klinik für Neurologie, Charité – Universitätsmedizin Berlin, Berlin
  • Philipp Euskirchen - Klinik für Neurologie, Charité – Universitätsmedizin Berlin, Berlin
  • Christoph Harms - Klinik für Neurologie, Charité – Universitätsmedizin Berlin, Berlin
  • Seija Lehnardt - Klinik für Neurologie, Charité – Universitätsmedizin Berlin, Berlin
  • Susanne A. Wolf - FG Zelluläre Neurowissenschaften, Max Delbrück Centrum Berlin-Buch, Berlin
  • Helmut Kettenmann - FG Zelluläre Neurowissenschaften, Max Delbrück Centrum Berlin-Buch, Berlin
  • Michael Synowitz - FG Zelluläre Neurowissenschaften, Max Delbrück Centrum Berlin-Buch, Berlin; Klinik für Neurochirurgie, Charité – Universitätsmedizin Berlin, Berlin

Deutsche Gesellschaft für Neurochirurgie. 65. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Dresden, 11.-14.05.2014. Düsseldorf: German Medical Science GMS Publishing House; 2014. DocDI.16.06

doi: 10.3205/14dgnc223, urn:nbn:de:0183-14dgnc2237

Veröffentlicht: 13. Mai 2014

© 2014 Dildar a Dzaye et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.

Gliederung

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Objective: Malignant gliomas are the most frequent primary tumors of the brain with poor clinical prognosis. Infiltrating peripheral macrophages and resident microglia that constitute the dominant tumor-infiltrating cells in glioblastoma are induced by the glioma cells to become immunosuppressive and tumor supportive. Glioma-initiating cells (GIC) could potentially promote this pro-tumorigenic phenotype. Exploring the interaction between GIC and glioma associated microglia/macrophages (GAM) may offer us an opportunity to further understand the cellular and molecular features of the GIC niche. In this study, we investigate the potential of GIC versus bulk cells to induce a pro-tumorigenic microglial cytokine profile.

Method: In the present study we stimulated primary cultured microglia with glioma conditioned medium (GCM) from GICs enriched or depleted GL261 cells and cytokine levels were determined by FlowCytomix.

Results: An almost 4-fold upregulation in microglial IL-6 secretion was observed using GCM from GICs while the secretion was unchanged with GCM from GICs depleted GL261 cells. Since Toll-like receptors are pattern recognition receptors that are responsible for pro-inflammatory cytokines release, we screened through all the TLRs and identified TLR4 as the main TLR controlling microglial IL-6 secretion. IL-6Rα and gp130 are highly expressed in GICs but not in microglial cells. The implantation of GL261-EGFP cells into IL-6 -/- mice resulted in significantly smaller tumors as compared to wild-type control mice. IL-6 and IL-6Rα are also expressed in human gliomas (which contain up to 30% microglia/macrophages) and inversely correlates with patient survival.

Conclusions: Our results show that GICs, but not the bulk glioma cells initiate microglial IL-6 secretion. IL-6 in turn promotes glioma cell growth and invasion.