title: IL-6 is required for glioma development in a mouse model.
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.
authors.affiliation: Division of Neuropathology, Institute of Pathology, University of Bern, Murtenstrasse 31, Bern CH-3010, Switzerland. weissenb@patho.unibe.ch
authors.forename: Jakob
authors.initials: J
authors.lastname: Weissenberger
authors.forename: Sébastien
authors.initials: S
authors.lastname: Loeffler
authors.forename: Andreas
authors.initials: A
authors.lastname: Kappeler
authors.forename: Manfred
authors.initials: M
authors.lastname: Kopf
authors.forename: Anton
authors.initials: A
authors.lastname: Lukes
authors.forename: Tatiana A
authors.initials: TA
authors.lastname: Afanasieva
authors.forename: Adriano
authors.initials: A
authors.lastname: Aguzzi
authors.forename: Joachim
authors.initials: J
authors.lastname: Weis
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000032:analysis / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis / Q000235:genetics / Q000502:physiology; D005910:Glioma / Q000209:etiology* / Q000473:pathology; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000502:physiology; D011230:Precancerous Conditions / Q000209:etiology; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000032:analysis / Q000502:physiology; D019076:Transgenes; D019061:src-Family Kinases / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D019061:src-Family Kinases