gms | German Medical Science

61st Annual Meeting of the German Society of Neurosurgery (DGNC) as part of the Neurowoche 2010
Joint Meeting with the Brazilian Society of Neurosurgery on the 20 September 2010

German Society of Neurosurgery (DGNC)

21 - 25 September 2010, Mannheim

Activated microglia cells colonize the perivascular niche and express pro-angiogenic factors in glioblastoma

Meeting Abstract

  • Kati Turkowski - Abteilung Neurochirurgie, Institut für Experimentelle Neurochirurgie, Charité-Universitätsmedizin Berlin, Germany
  • Susan Brandenburg - Abteilung Neurochirurgie, Institut für Experimentelle Neurochirurgie, Charité-Universitätsmedizin Berlin, Germany
  • Yordan Todorov Radev - Abteilung Neurochirurgie, Institut für Experimentelle Neurochirurgie, Charité-Universitätmedizin Berlin
  • Andreas Hippe - Abteilung Dermatologie, Universitätsklinikum Düsseldorf, Germany
  • Bernhard Homey - Abteilung Dermatologie, Universitätsklinikum Düsseldorf, Germany
  • Peter Vajkoczy - Abteilung Neurochirurgie, Institut für Experimentelle Neurochirurgie, Charité-Universitätsmedizin Berlin, Germany

Deutsche Gesellschaft für Neurochirurgie. 61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010. Mannheim, 21.-25.09.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocV1623

DOI: 10.3205/10dgnc096, URN: urn:nbn:de:0183-10dgnc0969

Published: September 16, 2010

© 2010 Turkowski et al.
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Outline

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Objective: Microglia cells represent the immune system of the mammalian brain and constitute up to one third of the brain tumor compartment. Nevertheless, the role of microglia in glioblastoma has remained unclear. The aim of our research is to investigate the microglia-tumor-interaction, especially the role of microglia on tumor angiogenesis.

Methods: First, we have studied the phenotype and contribution of microglia cells in the tumor area. Therefore, we implanted intracranially GL261 tumor cells into syngeneic mice. The analysis was performed by immunofluorescence staining in sections from these brains. Second, we purified microglia cells of naïve and tumor bearing mice by MACS technology. These isolated cells were used for RNA extraction following Realtime-PCR of pro-angiogenic factors. In addition, the microglia cells were cultivated in vitro and immunostained to determine their phenotype

Results: We found an increased number of microglia cells in the tumor area, expressing Iba-1, CD11b and CD68. These Iba-1+ cells showed a preference for the perivascular niche particularly in the tumor rim, the region with the highest angiogenic activity. Furthermore, we isolated CD11b+ cells from mice brains with a purity of more than 93%. The expression analysis of these cells from tumor bearing mice showed an upregulation of pro-angiogenic factors (e.g. angptl6, stc1, flt1). Moreover, we could mimic the situation of microglia in the tumor area by cultivating microglia cells with tumor-conditioned medium in vitro. In this case, stimulated microglia displayed an activated phenotype in contrast to naïve cells.

Conclusions: Our study suggests that the intrinsic immune system of the CNS is involved in tumor angiogenesis in malignant glioma. According to our model tumor cells activate microglia cells, which then localize to the perivascular niche and stimulate blood vessel growth.