gms | German Medical Science

60th Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Benelux countries and Bulgaria

German Society of Neurosurgery (DGNC)

24 - 27 May 2009, Münster

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Low grade glioma invasion is dependent on microglia

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  • D. Markovic - Neurochirurgie, Helios-Klinikum Berlin-Buch
  • C. Sridhar - Max Delbrück Zentrum Berlin
  • S. Michael - Neurochirurgie, Charité – Universitätsmedizin Berlin
  • K. Jürgen - Neurochirurgie, Helios-Klinikum Berlin-Buch
  • G. Rainer - Max Delbrück Zentrum Berlin
  • K. Helmut - Max Delbrück Zentrum Berlin

Deutsche Gesellschaft für Neurochirurgie. 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien. Münster, 24.-27.05.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. DocP12-03

doi: 10.3205/09dgnc377, urn:nbn:de:0183-09dgnc3776

Published: May 20, 2009

© 2009 Markovic et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Objective: We have shown previously that the microglia surrounding glioma is promoting glioma invasiveness by activation of MMP-2 (Markovic et al. 2005). Now we investigate whether microglial expression of membrane type 1 metalloprotease (MT1-MMP) is regulated by gliomas.

Methods: We used immunohistochemistry, the in vivo mouse GL261 glioma model, organotypical brain slice cultures, PCR, Western Blot, shRNA microglia transfection and MT1-MMP activity assays in cell culture experiments to demonstrate overexpression of MT1-MMP in microglia after glioma stimulation.

Results: MT1-MMP is upregulated in glioma associated microglia, but not in the glioma cells. Overexpression of MT1-MMP is even lethal for glioma cells. Glioma-released factors trigger the expression and activity of MT1-MMP in cultured microglial cells, mainly via a p38 MAP kinase pathway. Microglial MT1-MMP in turn activates glioma derived pro-MMP-2 and promotes glioma expansion, as shown in an ex vivo model using MT1-MMP deficient brain tissue and a microglia depletion paradigm. The antibiotic minocycline, a blood brain barrier penetrating blocker of microglial activation and p38 MAPK signaling pathway, interferes with MT1-MMP expression and activity in glioma associated microglia and attenuates glioma expansion in an in vivo model (GL261).

Conclusions: Glioma released factor is stimulating overexpression of MT1-MMP via p38 MAPK, which in turn leads to overproduction of active MMP-2. Minocycline treatment could have beneficial effects on glioma invasiveness.