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 c iliary neurotrophic factor and leukemia inhibitory factor, can induce diffe rentiation of glial cells. We have recently described that OSM inhibited th e growth of human glioma cells in vitro and induced a cell morphology resem bling that of mature astrocytes, Using the glioblastoma cell line 86HG39, w e demonstrated that treatment of the glioma cells with OSM also leads to a differentiation of the malignant glioma cells as judged by a strong increas e in glial fibrillary acidic protein expression. The differentiation and th e growth inhibition were not significantly blocked by expression of a domin ant-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-mito gen-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 cytoki ne.