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IL-6 is required for glioma development in a mouse model

Oncogene volume 23, pages 3308–3316 (2004)Cite this article

Abstract

The pleiotropic cytokine interleukin-6 (IL-6) contributes to malignant progression and apoptosis resistance of various cancer types. Although IL-6 is elevated in malignant gliomas, and glioma cells respond to IL-6, its functional role in gliomagenesis is unclear. We have investigated this role of IL-6 in a mouse model of spontaneous astrocytoma by crossbreeding glial fibrillary acidic protein (GFAP)-viral src oncogene transgenic mice with IL-6-deficient mice. We show here that ablation of IL-6 prevents tumour formation in these predisposed animals, but did not affect preneoplastic astrogliosis. Moreover, we demonstrate phosphorylation and nuclear translocation of the transcription factor signal transducer and activator of transcription (STAT)3, a prerequisite for IL-6 signalling, in 51 human gliomas WHO grade II–IV and all experimental mouse tumours investigated. Together with the observation that STAT3 activation increases with malignancy, these findings indicate an important role for IL-6 in the development and malignant progression of astrocytomas.

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Acknowledgements

We thank M Economou for excellent technical assistance and WR Hess for artwork. We are grateful to C Müller and PC Heinrich for discussions and to JP Steinbach for critically reading the manuscript. This work was supported by grants from the Bernese Cancer League and from the Dr med hc Erwin Braun Foundation, Basel, to JW and JW.

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Authors and Affiliations

  1. Division of Neuropathology, Institute of Pathology, University of Bern, Murtenstrasse 31, Bern, CH-3010, Switzerland

    Jakob Weissenberger, Sébastien Loeffler, Andreas Kappeler & Joachim Weis

  2. Department of Environmental Sciences, Molecular Biomedicine, Swiss Federal Institute of Technology, Wagistr. 27, Zurich-Schlieren, CH-8952, Switzerland

    Manfred Kopf

  3. Department of Neurosurgery, Inselspital, University of Bern, Bern, CH-3010, Switzerland

    Anton Lukes

  4. Institute of Neuropathology, University of Zurich, Schmelzbergstrasse 12, Zurich, CH-8091, Switzerland

    Tatiana A Afanasieva & Adriano Aguzzi

  5. Institute of Neuropathology, University Hospital, RWTH, Aachen, D-52074, Germany

    Joachim Weis

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  1. Jakob Weissenberger
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Correspondence to Jakob Weissenberger.

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Weissenberger, J., Loeffler, S., Kappeler, A. et al. IL-6 is required for glioma development in a mouse model. Oncogene 23, 3308–3316 (2004). https://doi.org/10.1038/sj.onc.1207455

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