Divergent effects of oncostatin M on astroglioma cells: Influence on cell proliferation, invasion, and expression of matrix metalloproteinases

Abstract

Oncostatin M (OSM), a cytokine of the interleukin-6 (IL-6) family, can either promote or inhibit cell growth in various normal and tumor cells. We addressed the effects of exogenous OSM on the proliferation and invasion of human astroglioma cells. In addition, we investigated one of the possible mechanisms involved: modulation of matrix metalloproteinase (MMP) expression and enzymatic activity. We found that OSM inhibited the proliferation of two human astroglioma cell lines (CH235-MG and U87-MG), and that this effect was not due to apoptosis. The inhibitory effect of OSM on proliferation was mediated through the gp130/OSMRbeta receptor complex. To extend these findings, we analyzed the effects of OSM on primary tumor cells from glioblastoma patients. OSM suppressed the proliferation of primary glioblastoma cells, but not that of normal astrocytes. Interestingly, OSM did not suppress astroglioma cell invasion. This may be due to the differential regulation of MMPs by OSM. We found that OSM inhibited the constitutive expression of MMP-2, while MMP-9 expression was enhanced in astroglioma cell lines. We conclude that OSM inhibits proliferation of human astroglioma cells and primary glioblastoma cells via the gp130/OSMRbeta receptor complex. However, OSM does not affect the invasive capacity of the astroglioma cells, which may be due to the divergent effects of OSM on MMP-2 and MMP-9 expression. Collectively, these findings suggest a complex role for OSM in astroglioma biology.

Signal Transducer and Activator of Transcription-3: A Molecular Hub for Signaling Pathways in Gliomas

“…In some glioblastoma cell lines, autocrine IL-6 expression resulted in constitutive activation of STAT-3, and neutralizing antibodies to IL-6 reduced STAT-3 activation, inhibited cell proliferation, and induced apoptosis (48). In a number of other human brain tumor cell lines, stimulation with IL-6, leukemia inhibitory factor, ciliary neurotrophic factor, or OSM resulted in induced STAT-3 activation (46), and treatment of human astroglioma cells with OSM increased the STAT-3 -dependent expression and activation of matrix metalloproteinase-9 and VEGF (59,60).…”

IL-6 augments the invasiveness of U87MG human glioblastoma multiforme cells via up-regulation of MMP-2 and fascin-1

“…In the last fifty years, multimodality therapy has achieved only modest gains for malignant gliomas (1), which is one of the most common and fatal primary tumors in adults (2) and the second cause of cancer-related death in the young adults (3). It is generally believed that invasion and angiogenesis both play critical roles in the formation of recurrent tumors (4).…”

Oncostatin M-induced genes in human astrocytomas

“…Further analysis showed that the tumor cells have functional OSM receptors and signal transduction systems, but the effects of OSM expression on proliferation, apoptosis and migration in brain tumors remain unclear (7,14,20,21). In this study we used a genome wide microarray analysis to investigate the expression patterns of OSM responsive genes in U1242MG.…”

“…OSM is a member of the interleukin (IL)-6 cytokine family which includes IL-6, IL-11, leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1) and cardiotrophin-like cytokine (CLC) (7,8). These cytokines are involved in the regulation of the acute-phase to injury, infection, haematopoiesis, liver and neuronal regulation, embryonal development and fertility (9).…”