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

CX3CL1-CX3CR1 mediated cross talk between glioma infiltrating microglia (GIMs) and human glioma cells promotes GIM recruitment

Meeting Abstract

  • K. Hattermann - Anatomisches Institut, Campus Kiel, Universitätsklinikum Schleswig-Holstein, Kiel
  • R. Mentlein - Klinik für Neurochirurgie, Campus Kiel, Universitätsklinikum Schleswig-Holstein, Kiel
  • F. Knerlich-Lukoschus - Klinik für Neurochirurgie, Campus Kiel, Universitätsklinikum Schleswig-Holstein, Kiel
  • M. Mehdorn - Klinik für Neurochirurgie, Campus Kiel, Universitätsklinikum Schleswig-Holstein, Kiel
  • J. Held-Feindt - Klinik für Neurochirurgie, Campus Kiel, Universitätsklinikum Schleswig-Holstein, Kiel

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. DocMI.05-08

doi: 10.3205/09dgnc199, urn:nbn:de:0183-09dgnc1997

Published: May 20, 2009

© 2009 Hattermann et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Objective: A significant characteristic of the highly malignant glioblastoma brain tumors is the marked presence of glioblastoma infiltrating microglia/macrophages (GIMs). Since microglia cells are known to express the fraktalkine receptor CX3CR1 and astrocytes are noted for CX3CL1 expression itself under non-pathological conditions, the goal of the present study is to investigate the CX3CL1-CX3CR1 expression pattern and cross-talk in human glioma samples.

Methods: CX3CL1 and CX3CR1 mRNA expression were examined using real-time reverse transcription polymerase chain reaction (qRT-PCR). Protein expression was determined by immunohistochemistry, fluorescence staining, ELISA and Western blotting techniques. Isolation of GIMs from fresh human glioblastoma samples was performed with CD11b MACS technology, and expression pattern of CX3CL1-CX3CR1 and cell-specific markers was investigated by qRT-PCR. Using a co-culture system composed of GIMs and the corresponding glioma cells of the same tumor sample GIMs could be cultured and expanded. Cell adhesion of cultured GIMs on a glioma cell was examined in presence of CX3CL1 / vehicle followed by immunocytochemistry.

Results: We could show CX3CR1 was significantly overexpressed both on mRNA and protein level in astrocytomas and glioblastomas that in relation to normal brain tissue, whereas CX3CL1 expression pattern remains unchanged. Double/triple-immunofluorescence investigations indicated a co-staining of CX3CL1 within GFAP-expressing glioblastoma regions. CX3CR1 was found on CD11b/CD11c and Iba1 positive GIMs. In contrast to corresponding GFAP and CX3CL1 positive glioma cells, that in relation to normal brain tissue freshly isolated CD11b positive GIMs of the same tumor sample were characterized by a high expression pattern of CX3CR1 and Iba1. CX3CL1 promotes cell adhesion of cultured GIMs onto a confluent cell layer of glioma cells in the same range as determined for THP1 monocytes, and this effect could be abolished by preabsorption with a specific anti-CX3CL1 antibody.

Conclusions: These findings provide evidence that glioma-produced CX3CL1 promotes GIM recruitment via its receptor CX3CR1 which favours GIM adhesion and infiltration to glioma cell populations.