Oncostatin M-mediated growth inhibition of human glioblastoma cells does not depend on stat3 or on mitogen-activated protein kinase activation.
Oncostatin M (OSM) and other members of the interleukin-6 cytokines, like ciliary neurotrophic factor and leukemia inhibitory factor, can induce differentiation of glial cells. We have recently described that OSM inhibited the growth of human glioma cells in vitro and induced a cell morphology resembling that of mature astrocytes. Using the glioblastoma cell line 86HG39, we demonstrated that treatment of the glioma cells with OSM also leads to a differentiation of the malignant glioma cells as judged by a strong increase in glial fibrillary acidic protein expression. The differentiation and the growth inhibition were not significantly blocked by expression of a dominant-negative (dn) signal transducer and activator of transcription (Stat) 3 protein. OSM exerted a reduction in DNA synthesis even in the presence of a high expression level of dnStat3. Moreover, inhibition of the ras-raf-mitogen-activated protein kinase (MAPK) pathway by the MAPK kinase 1 inhibitor PD98059 resulted in a synergistic enhancement of the OSM effect, indicating that the activation of this pathway counteracts the activity of the cytokine.
Department of Neurology, Westfälische Wilhelms-Universität Münster, Germany. halfter@uni-muenster.de
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D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D005909:Glioblastoma; D005910:Glioma; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D018121:Receptors, Cytokine / Q000235:genetics / Q000502:physiology*; D053677:Receptors, Oncostatin M; D011994:Recombinant Proteins / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; C508351:OSM protein, human; D010455:Peptides; D018121:Receptors, Cytokine; D053677:Receptors, Oncostatin M; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D053683:Oncostatin M; D020928:Mitogen-Activated Protein Kinases