gms | German Medical Science

55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

25. bis 28.04.2004, Köln

Dominant-negative inhibition of the receptor tyrosine kinase AXL suppresses glioma cell migration and invasion, and prolongs survival

Dominant-negative Blockade der Rezeptor-Tyrosinkinae AXL unterdrückt Gliomzell-Migration und -Invasion und verlängert das Überleben

Meeting Abstract

  • corresponding author Peter Vajkoczy - Neurochirurgische Klinik, Universitätsklinikum Mannheim, Mannheim
  • R. Erber - Neurochirurgische Klinik, Universitätsklinikum Mannheim, Mannheim
  • H. H. Capelle - Neurochirurgische Klinik, Universitätsklinikum Mannheim, Mannheim
  • U. Eichelsbacher - Max-Planck-Institut für Biochemie, Martinsried
  • A. Ullrich - Max-Planck-Institut für Biochemie, Martinsried

Deutsche Gesellschaft für Neurochirurgie. Ungarische Gesellschaft für Neurochirurgie. 55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie. Köln, 25.-28.04.2004. Düsseldorf, Köln: German Medical Science; 2004. DocP 05.51

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2004/04dgnc0334.shtml

Veröffentlicht: 23. April 2004

© 2004 Vajkoczy 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 vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective

Receptor tyrosine kinases (RTKs) play an important role in growth and progression of brain tumors. Our previous work has shown that the RTK AXL, whose biological function has remained obscure so far, is overexpressed by glioma cell lines. The aim of the present study was to analyse the role of AXL in glioma biology.

Methods

Two glioma cell lines, one expressing high levels of AXL (i.e. SF126) and the other lacking intrinsic AXL (i.e. SF767) were transfected to overexpress either the human wild-type form (AXL-WT) or a truncated, dominant-negative mutant form (AXL-DN). Glioma cell morphology and cell behavior with respect to proliferation, aggregability, migration, and invasion were assessed in vitro. To study the relevance of AXL for tumor growth the glioma cell lines were implanted subcutaneously and into the brains of nude mice. Finally, glioma cells were implanted into the dorsal skinfold chamber model to assess tumor cell behavior, tumor angiogenesis, and tumor perfusion in vivo by intravital multi-fluorescence microscopy.

Results

SF126-AXL-DN cells were characterized by reduced cell-to-cell contacts, a moderately reduced proliferative activity, and most importantly by a severe impairment of tumor cell migration and tumor cell invasion. In vivo, subcutaneous SF126-AXL-DN tumor growth was reduced by 97% und tumor cell invasion into the adjacent tissue was suppressed. Finally, survival following intracerebral implantation of SF126-AXL-DN cells was significantly prolonged compared to SF126-AXL-WT cells. In contrast, inhibition of AXL signaling in SF767 cells had no significant effects.

Conclusions

Our study provides evidence that AXL modulates migration and invasion of glioma cells and that inhibition of AXL signalling suppresses tumor expansion by blocking tumor cell invasion. AXL may represent a novel target for the treatment of malignant glioma.