gms | German Medical Science

56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
3èmes journées françaises de Neurochirurgie (SFNC)

Deutsche Gesellschaft für Neurochirurgie e. V.
Société Française de Neurochirurgie

07. bis 11.05.2005, Strasbourg

Glioblastoma angiogenesis and invasion are inhibited by combination treatments directed against VEGFR-2, EGFR and VE-cadherin

Inhibierung der Angiogenese und Invasion von Glioblastomen durch kombinierte Antagonisierung von VEGFR-2, EGFR und VE-Cadherin

Meeting Abstract

  • corresponding author K. Lamszus - Neurochirurgische Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg
  • M. A. Brockmann - Neurochirurgische Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg
  • C. Eckerich - Neurochirurgische Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg
  • P. Bohlen - ImClone Systems, New York/USA
  • C. May - ImClone Systems, New York/USA
  • M. Westphal - Neurochirurgische Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg

Deutsche Gesellschaft für Neurochirurgie. Société Française de Neurochirurgie. 56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3èmes journées françaises de Neurochirurgie (SFNC). Strasbourg, 07.-11.05.2005. Düsseldorf, Köln: German Medical Science; 2005. Doc10.05.-08.04

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2005/05dgnc0123.shtml

Veröffentlicht: 4. Mai 2005

© 2005 Lamszus 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

Text

Objective

Increasing evidence suggests that inhibition of tumour angiogenesis can influence tumour cell invasion and metastasis. We previously showed that systemic antagonisation of vascular endothelial growth factor receptor-2 (VEGFR-2) with the monoclonal antibody (mAb) DC101 inhibited glioblastoma growth in an orthotopic model, but caused increased tumour cell invasion along the preexistent vasculature.

Methods

In human glioblastoma cells signalling through the epidermal growth factor receptor (EGFR) predominantly stimulates tumour cell invasion. Therefore, we attempted to inhibit tumour cell invasion caused by DC101 therapy by combined systemic treatment with a mAb against EGFR (C225). In addition, we analysed whether antagonisation of vascular endothelial (VE)-cadherin as a different anti-angiogenic target can also inhibit glioblastoma growth and whether this also stimulates invasion. Treatments were either initiated on day 1 after intracerebral tumour cell injection or on day 6 when tumours were already established.

Results

Increased tumour cell invasion caused by DC101 monotherapy was inhibited by 50-66% through combined treatment with C225 and DC101. C225 inhibited glioblastoma cell migration in vitro, but had no effect on the volume of the main tumour mass or on tumour cell proliferation or apoptosis in vivo, neither alone nor in combination with DC101. The anti-VE-cadherin mAb E4G10 also inhibited tumour angiogenesis and growth, although with weaker effects than DC101, and the effects of E4G10 were dependent on early initiation of treatment. E4G10 treatment caused increased tumour cell invasion along the host vasculature, although with less effect than DC101.

Conclusions

Our findings show that anti-angiogenic glioblastoma therapy targeting either VEGFR-2 or VE-cadherin can inhibit tumour growth, but can increase tumour cell invasion in an orthotopic model. The increased tumour cell invasion caused by DC101 treatment can be inhibited by simultaneous antagonisation of EGFR which in the context of human glioblastomas has been implicated in tumour cell invasion.