gms | German Medical Science

58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

26. bis 29.04.2007, Leipzig

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A1 adenosine receptor activity on microglial cells modulates the growth of experimental glioblastoma cells via MMP regulation

A1-Adenosinrezeptoraktivität auf Mikrogliazellen modulieren das Wachstum experimenteller Glioblastome via Regulation von MMP's

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  • corresponding author M. Synowitz - Klinik für Neurochirurgie, HELIOS Klinikum Berlin, Berlin, Deutschland
  • R. Glass - Zelluläre Neurowissenschaften, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland
  • K. Farber - Zelluläre Neurowissenschaften, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland
  • D. Markovic - Klinik für Neurochirurgie, HELIOS Klinikum Berlin, Berlin, Deutschland
  • G. Kronenberg - Klinik für Psychiatrie und Psychotherapie, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Deutschland
  • K. Herrmann - Zelluläre Neurowissenschaften, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland
  • J. Schnermann - National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health, Bethesda, USA
  • C. Nolte - Zelluläre Neurowissenschaften, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland
  • N. van Rooijen - Molecular Department of Molecular Cell Biology, University of Amsterdam, Amsterdam, The Netherlands
  • J. Kiwit - Klinik für Neurochirurgie, HELIOS Klinikum Berlin, Berlin, Deutschland
  • H. Kettenmann - Zelluläre Neurowissenschaften, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC). Leipzig, 26.-29.04.2007. Düsseldorf: German Medical Science GMS Publishing House; 2007. DocP 086

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2007/07dgnc341.shtml

Published: April 11, 2007

© 2007 Synowitz 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: In the present study, we have addressed the question whether deletion of A1 adenosine receptors affect glioblastoma – host interaction observed in A1AR deficient mice.

Methods: G261 glioblastoma cells were inoculated into A1AR-/- mice and A1AR+/+ littermate controls. With this approach, we deleted the A1AR in the host cells, but not in the inoculated GL261 glioblastoma cells. Animals were sacrificed 14 days after GL261 inoculation and the tumor area was determined double-blinded in axial section at the maximal diameter. Immunofluorescent triple labeling was carried out on 40-µm-free-floating sections using a spectral confocal microscope.

Results: The tumor size in A1AR-/- mice was significantly larger as compared to A1AR+/+ mice (mean±SE, 0.96±0.09 mm for control (n=73); 1.69±0.03 mm for A1AR-/- mice (n=99)). To analyze the cell populations from the host in the vicinity of the tumor cells, we studied the distribution of microglial cells and astrocytes in A1AR-/- and A1AR+/+ mice. Immunoreactivity for the macrophage / microglia marker Iba-1 revealed an accumulation of Iba-1 positive cells at the tumor border. In A1AR-/- mice the density and number of Iba-1 positive cells was significantly higher as compared to wild-type littermates. No differences in the GFAP-positive cell population was observed comparing A1AR-/- and A1AR+/+. In gelatin zymographies, we observed that microglia abundantly release active MMP-2 after stimulation with glioma conditioned medium. The glioma-stimulated increase in MMP-2 activity was blunted by costimulation with 100 µmol/L adenosine.

Conclusions: These results imply that A1AR modulate tumor growth and that microglial cells are the cellular candidates to mediate this effect.

*Authors 1, 2, 3 equally contributed to this work