gms | German Medical Science

59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

01. - 04.06.2008, Würzburg

Inhibition of glioblastoma growth in a highly invasive nude mouse model

Inhibierung des Glioblastomwachstums in einem hoch invasiven Nacktmausmodell

Meeting Abstract

  • corresponding author T. Martens - Neurochirurgische Klinik, Labor für Hirntumorbiologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg
  • Y. Laabs - Neurochirurgische Klinik, Labor für Hirntumorbiologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg
  • H. S. Günther - Neurochirurgische Klinik, Labor für Hirntumorbiologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg
  • M. Westphal - Neurochirurgische Klinik, Labor für Hirntumorbiologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg
  • K. Lamszus - Neurochirurgische Klinik, Labor für Hirntumorbiologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg

Deutsche Gesellschaft für Neurochirurgie. Società Italiana di Neurochirurgia. 59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch). Würzburg, 01.-04.06.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. DocDI.03.07

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2008/08dgnc164.shtml

Veröffentlicht: 30. Mai 2008

© 2008 Martens et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

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Objective: A major shortcoming of traditional mouse models based on xenografted human glioblastoma cells is that tumor cells do not invade. Another deficit is that genetic alterations, such as amplification of the epidermal growth factor receptor (EGFR), are typically not maintained in glioma cell lines and xenografts derived thereof. These models are therefore of limited value for preclinical therapeutic studies.

Methods: We established a highly invasive orthotopic mouse model using freshly resected glioblastoma tissue, briefly cultured as spheroids and injected into the brains of nude mice. Animals were treated for 4 weeks with either interstitial infusion of a monoclonal antibody against the EGFR (antibody C225) or with intraperitoneal injections of an antibody against the vascular endothelial growth factor receptor-2 (VEGFR-2, antibody DC101). Tumor extension was measured using image analysis on H&E-stained serial sections, defining 36 landmark points at 6 different coronal levels with 6 different areas each (e.g. striatum, corpus callosum, thalamus).

Results: Highly invasive xenografts were obtained from 9 different glioblastomas. Of 7 different xenograft-cases treated with C225, 3 responded to treatment with significant tumor growth inhibition, whereas 4 did not. All responsive tumors were derived from glioblastomas exhibiting EGFR gene amplification as well as the truncated EGFRvIII variant. EGFR amplification was maintained in mouse xenografts by FISH analysis. The proportion of apoptotic cells was increased in responding tumors, whereas the fraction of proliferating cells was decreased. All non-responsive tumors lacked EGFR amplification and EGFRvIII. None of 4 xenograft cases treated with DC101 responded to treatment, and quantification of intratumoral blood vessels showed that the diffusely invading tumors grew largely independent of angiogenesis.

Conclusions: This is the first study showing that inhibition of invasive glioblastoma growth can be achieved in vivo using interstitial delivery of an anti-EGFR antibody. Importantly, tumor responsiveness depended on the presence of amplified and mutated EGFR. In contrast, anti-angiogenic treatment was not effective against the diffusely invading tumors.