gms | German Medical Science

58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

26. bis 29.04.2007, Leipzig

Upregulation of cytokine activated IL6-r/STAT3 signalling correlates with glioma grade

Hochregulation der Zytokine-aktivierten IL6-r/STAT3 Signalkaskade korreliert mit dem WHO-Grad von Gliomen

Meeting Abstract

  • corresponding author N. Thon - Neurochirurgische Klinik und Poliklinik, Klinikum Großhadern, Ludwig-Maximilians-Universität, München
  • M. Duy - Neurochirurgische Klinik und Poliklinik, Klinikum Großhadern, Ludwig-Maximilians-Universität, München
  • J. Hegermann - Neurochirurgische Klinik und Poliklinik, Klinikum Großhadern, Ludwig-Maximilians-Universität, München
  • O. Schnell - Neurochirurgische Klinik und Poliklinik, Klinikum Großhadern, Ludwig-Maximilians-Universität, München
  • J.-C. Tonn - Neurochirurgische Klinik und Poliklinik, Klinikum Großhadern, Ludwig-Maximilians-Universität, München
  • R. Goldbrunner - Neurochirurgische Klinik und Poliklinik, Klinikum Großhadern, Ludwig-Maximilians-Universität, München

Deutsche Gesellschaft für Neurochirurgie. 58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC). Leipzig, 26.-29.04.2007. Düsseldorf: German Medical Science GMS Publishing House; 2007. DocP 087

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2007/07dgnc342.shtml

Veröffentlicht: 11. April 2007

© 2007 Thon 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: The family of interleukin-6 type cytokines (e.g. IL-6, oncogene M, CNTF and LIF) has pleiotrophic effects on a variety of different cell types and activate target genes involved in cell survival, proliferation and inhibition of apoptosis via IL-6 receptor activated STAT3 signalling, indicating an important role of IL6-r/STAT3 in tumour development and progression. Although IL-6 expression in gliomas has been reported so far, no data has been published on the expression and activation of the IL6-r/STAT3 signalling pathway in gliomas of different grades so far.

Methods: In order to asses IL-6 receptor mediated activation of STAT3 signalling in gliomagenesis we investigated the expression of the IL6-r single transmembrane proteins gp80, gp130 and LIFα and the downstream activation of STAT3 by specific phosphorylation (S727) in tissue samples of human gliomas WHO° II-IV (n=10) and non-neoplastic brain tissues (n=5) using IHC, Western Blot and RT-PCR analysis. The effects of IL6 incubation on the proliferation of primary cell cultures harvested from human glioblastomas and non neoplastic brain tissues have been analysed using BrdU-labelling in vitro.

Results: IHC and Western blot analysis revealed a constitutive upregulation and cellular co-expression of IL6-r proteins gp80, gp130 and LIFα correlating with glioma grade compared to normal brain tissue controls. Furthermore an increasing proportion of ubiquitously expressed STAT3 showed specific IL6-r mediated activation by phosphorylation at serine 727 residues again correlating with WHO grade. In vitro IL-6 family cytokine stimulation significantly increased proliferation of primary cell cultures from WHO°IV gliomas compared to non neoplastic brain controls.

Conclusions: Here we report for the first time the constitutive expression and activation of IL6-r/STAT3 signalling correlating with glioma grade with proliferation enhancing effects of IL-6 stimulation in vitro. We hypothesize that selective activation of the IL6-r/STAT3 signalling significantly contributes to tumour cell proliferation and might play a crucial role in the malignant alterations in gliomas of different grades.