gms | German Medical Science

67. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Koreanischen Gesellschaft für Neurochirurgie (KNS)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

12. - 15. Juni 2016, Frankfurt am Main

Microglia as a therapeutical target in malignant gliomas

Meeting Abstract

  • Darko S. Markovic - Helios Klinikum Buch, Neurochirurgie, Berlin, Germany; Max Delbrück Zentrum für Molekulare Medizin, Zelluläre Neurowissenschaften, Berlin, Germany
  • M. Mersch - Max Delbrück Zentrum für Molekulare Medizin, Zelluläre Neurowissenschaften, Berlin, Germany
  • Helmut Kettenmann - Max Delbrück Zentrum für Molekulare Medizin, Zelluläre Neurowissenschaften, Berlin, Germany
  • Jürgen C. W. Kiwit - Helios Klinikum Buch, Neurochirurgie, Berlin, Germany

Deutsche Gesellschaft für Neurochirurgie. 67. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 1. Joint Meeting mit der Koreanischen Gesellschaft für Neurochirurgie (KNS). Frankfurt am Main, 12.-15.06.2016. Düsseldorf: German Medical Science GMS Publishing House; 2016. DocMI.13.06

doi: 10.3205/16dgnc310, urn:nbn:de:0183-16dgnc3106

Veröffentlicht: 8. Juni 2016

© 2016 Markovic et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Objective: Analysis of temozolomide, dexamethasone and minocycline on pro-tumorigenic properties of glioma infiltrating microglia (GIM) in mouse and human cell and tissue culture experimental models.

Method: We used RT-PCR, qPCR, ELISA and immunohistochemistry in mouse primary microglia cultures or in human glioma infiltrating CD11b+ cells (MACS sorted from human GBM samples) or in human glioblastoma tissue cultures to test effects of temozolomide, dexamethasone and minocycline on microglia properties important for glioma invasiveness, survival and immunosuppression.

Results: Using primary microglia and GIM we demonstrate that minocycline and dexamethasone or their combination reduce glioma stimulated microglial proliferation and diminish survival of microglia by inducing apoptosis. Moreover, minocycline and dexamethasone down-regulate release of active matrix metalloproteinase 2 (MMP-2) from glioma stimulated microglia. Further, we determined diminished secretion of IL-10 in microglia treated with minocycline and dexamethasone. Finally in a human glioblastoma tissue culture we confirm the effect of minocycline, dexamethasone and temozolomide to reduce proliferation of microglia and induce apoptosis in glioma cells.

Conclusions: Minocycline and dexamethasone treatment of mouse primary microglia and human GIM down-regulates microglial proliferation, MMP-2 activation and immunosuppression. Minocycline and dexamethasone are promising candidates for novel glioblastoma therapy by inhibiting microglial properties that promote glioblastoma development.