IL-6 is required for glioma development in a mouse model
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...
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Veröffentlicht in: | Oncogene 2004-04, Vol.23 (19), p.3308-3316 |
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Sprache: | eng |
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Zusammenfassung: | 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
s
ignal
t
ransducer and
a
ctivator of
t
ranscription (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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ISSN: | 0950-9232 1476-5594 |
DOI: | 10.1038/sj.onc.1207455 |