Oncostatin-M induction of vascular endothelial growth factor expression in astroglioma cells
- 6 November 2003
- journal article
- Published by Springer Nature in Oncogene
- Vol. 22 (50) , 8117-8124
- https://doi.org/10.1038/sj.onc.1206922
Abstract
Oncostatin-M (OSM), a hematopoietic cytokine, and vascular endothelial growth factor (VEGF), a quintessential angiogenic signal, are coexpressed in development, cancer and inflammation. Here, we report that OSM treatment of human astroglioma cell lines increases VEGF levels by approximately threefold. Interleukin-1beta (IL-1beta), in combination with OSM, induces up to sevenfold higher VEGF expression, without significantly inducing VEGF on its own. Specifically examining the OSM contribution to VEGF expression, neutralizing antibodies to OSM receptor subunits gp130 and OSMRbeta, but not LIFRbeta, inhibited OSM induction of VEGF, indicating that the OSM-specific receptor OSMRbeta/gp130 transduces the OSM signal for VEGF synthesis. OSM induction of VEGF promoter activity maps to the (-1171, -786) region of the VEGF promoter, which contains a STAT-3-binding site. STAT-3 is indeed essential for this response, since overexpression of a dominant-negative STAT-3 blocks OSM induction of VEGF promoter activity, as well as endogenous VEGF expression. Finally, we demonstrate that OSM is expressed in glioblastoma multiforme tumor biopsies, a particularly malignant form of brain tumor. This novel mechanism of VEGF regulation in astroglioma cells may be active in pathophysiological states where both OSM and IL-1beta are present.Keywords
This publication has 39 references indexed in Scilit:
- Insulin Stimulates Hypoxia-inducible Factor 1 through a Phosphatidylinositol 3-Kinase/Target of Rapamycin-dependent Signaling PathwayJournal of Biological Chemistry, 2002
- Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesisOncogene, 2002
- Induction of VEGF Gene Transcription by IL-1 β is Mediated Through Stress-activated MAP Kinases and Sp1 Sites in Cardiac MyocytesJournal of Molecular and Cellular Cardiology, 2000
- ONCOSTATIN M ACTIVATES STAT DNA BINDING AND TRANSCRIPTIONAL ACTIVITY IN PRIMARY HUMAN FETAL ASTROCYTES: LOW- AND HIGH-PASSAGE CELLS HAVE DISTINCT PATTERNS OF STAT ACTIVATIONCytokine, 2000
- Oncostatin M Regulation of Interleukin‐6 Expression in AstrocytesJournal of Neurochemistry, 2000
- Sp1 recognition sites in the proximal promoter of the human vascular endothelial growth factor gene are essential for platelet-derived growth factor-induced gene expressionOncogene, 1997
- Oncostatin M is a proinflammatory mediator. In vivo effects correlate with endothelial cell expression of inflammatory cytokines and adhesion molecules.Journal of Clinical Investigation, 1997
- Hyperplasia of Lymphatic Vessels in VEGF-C Transgenic MiceScience, 1997
- Induction of Vascular Endothelial Growth Factor by Tumor Necrosis Factor α in Human Glioma CellsJournal of Biological Chemistry, 1996
- Interleukin 6 Induces the Expression of Vascular Endothelial Growth FactorJournal of Biological Chemistry, 1996