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

Marked tumor growth by suppression of macrophage-mediated host defense in the C6 experimental glioma implantation model

Meeting Abstract

  • C. Herbold - Neurochirurgische Klinik der Universität Würzburg
  • C. Hagemann - Neurochirurgische Klinik der Universität Würzburg
  • C. Varallyay - Abteilung für Neuroradiologie der Universität Würzburg
  • N. van Rooijen - Institut für molekulare Zellbiologie, Freie Universität Amsterdam
  • K. Roosen - Neurochirurgische Klinik der Universität Würzburg
  • G. Vince - Neurochirurgische Klinik der Universität Würzburg

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. DocP06-08

doi: 10.3205/09dgnc312, urn:nbn:de:0183-09dgnc3124

Published: May 20, 2009

© 2009 Herbold 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: We showed that the C6 glioma orthotopically implanted into Sprague-Dawley rats will progress in the first 28 days, but within a time span of approximately 4 weeks will then regress again spontaneously. This phenomenon was independent of CD8+ and CD4+ T-lymphocytes. However, the role of tumor-associated macrophages in malignant gliomas remains elusive. In this study we investigated the role of macrophages in tumor invasion, control and spontaneous tumor regression in the C6 orthotopic tumor implantation model.

Methods: Reaggregated C6 spheroid tumors were implanted into the forebrain of 56 Sprague-Dawley rats. 24 tumors were implanted in thymectomized Sprague Dawley rats to minimize T-cell effects. In 24 animals macrophages were depleted using intraperitoneal liposome-encapsulated clodronate. The animals were examined by MRI at postoperative days 7, 14, 21, 28, 35 and 42. The MRI protocol included a T2-w and T1-w SE sequence before and after application of contrast medium and a 3D-CISS sequence for volumetry. A total of two animals was selected after each MR exam from both groups and sacrificed for immunohistochemistry.

Results: Tumors in the immunocompetent rats progressed to a maximum median volume of 150mm3 on day 28. In the thymectomized group the animals developed slightly bigger tumors of a maximum median volume of 178mm3. However, all animals displayed regressive patterns and tumor regression. The influx of macrophages was to be detected after day 7 post implantation. ED-1 macrophages consistently increased to reach a maximum in the tumor centers at day 21 post implantation. Macrophage depleted animals reached maximum tumor volume one week earlier on day 21 post implantation and showed an increased tumor progression to 5 times the size of the immunocompetent controls. Median tumor volume on MR was 766 mm3. Tumor regression remained suppressed in all but 2 animals, where an increased tolerance to clodronate with increased macrophage counts in the spleen was noted.

Conclusions: Tumors in the orthotopic C6 glioma model will progress between 21 to 28 days and then regress again spontaneously. Regression occurs independent from local CD8+ T-cell recruitment. Tumor regression is suppressed by clodronate macrophage depletion. In this model macrophage-mediated host defense is vital for tumor surveillance and control.