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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Toll-like receptor 2 mediates microglia/brain macrophage MT1-MMP expression and glioma expansion

Meeting Abstract

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  • Katyayni Vinnakota - Cellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany
  • Feng Hu - Cellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany
  • Min-Chi Ku - Cellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany
  • Petya B. Georgieva - Cellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany
  • Frank Szulzewsky - Cellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany
  • Andreas Pohlmann - Berlin Ultrahigh Field Facility, Max Delbrück Center for Molecular Medicine, Berlin, Germany
  • Sonia Waiczies - Berlin Ultrahigh Field Facility, Max Delbrück Center for Molecular Medicine, Berlin, Germany
  • Helmar Waiczies - Berlin Ultrahigh Field Facility, Max Delbrück Center for Molecular Medicine, Berlin, Germany
  • Thoralf Niendorf - Berlin Ultrahigh Field Facility, Max Delbrück Center for Molecular Medicine, Berlin, Germany
  • Seija Lehnardt - Department of Neurology and Center for Anatomy, Institute of Cell Biology and Neurobiology, Charité – Universitätsmedizin, Berlin, Germany
  • Uwe-Karsten Hanisch - Department of Neuropathology, University of Göttingen, Göttingen, Germany
  • Darko Markovic - Department of Neurosurgery, Helios Clinic, Berlin, Germany
  • Susanne A. Wolf - Cellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany
  • Rainer Glass - Neurosurgical Research, Clinic for Neurosurgery, Ludwig Maximilians University of Munich, Munich, Germany
  • Helmut Kettenmann - Cellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany
  • Michael Synowitz - Cellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany; Department of Neurosurgery, Charité – Universitätsmedizin, Berlin, Germany

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. DocP 066

doi: 10.3205/14dgnc462, urn:nbn:de:0183-14dgnc4622

Veröffentlicht: 13. Mai 2014

© 2014 Vinnakota 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

Text

Objective: Glioblastomas are the most aggressive primary brain tumors in humans. Microglia/brain macrophage accumulation in and around the tumor correlates with malignancy and poor clinical prognosis of these tumors. We have previously shown that microglia promote glioma expansion through upregulation of membrane type 1 matrix metalloprotease (MT1-MMP). This upregulation depends on signaling via the Toll-like receptor (TLR) adaptor molecule myeloid differentiation primary response gene 88 (MyD88).

Method: Using in vitro, ex vivo, and in vivo techniques, we identified TLR2 as the main TLR controlling microglial MT1-MMP expression and promoting microglia assisted glioma expansion.

Results: The implantation of mouse GL261 glioma cells into TLR2 knockout mice resulted in significantly smaller tumors, reduced MT1-MMP expression, and enhanced survival rates compared with wild-type control mice. Tumor expansion studied in organotypic brain slices depended on both parenchymal TLR2 expression and the presence of microglia. Glioma-derived soluble factors and synthetic TLR2 specific ligands induced MT1-MMP expression in microglia from wild-type mice, but no such change in MT1-MMP gene expression was observed in microglia from TLR2 knockout mice.We also found evidence that TLR1 and TLR6 cofunction with TLR2 as heterodimers in regulating MT1-MMP expression in vitro.

Conclusions: Our results thus show that activation of TLR2 along with TLRs 1 and/or 6 converts microglia into a glioma supportive phenotype.