Oncostatin-M induction of vascular endothelial growth factor expression in astroglioma cells

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

“…Tumors formed from FGFR dominantnegative expressing cells exhibited lower levels of VEGF compared with tumors from wild-type counterparts (70), which helps to explain why the dominant-negative FGFR-expressing tumors displayed slower growth rates. Interestingly, STAT-3 is a downstream transcriptional target of FGFR (69), and activation of STAT-3 results in expression of VEGF (59). These observations suggest that STAT-3 was the critical link between FGFR signaling and VEGF-mediated tumor growth in C6 glioma cells.…”

“…Several groups observed constitutive expression of IL-6 and OSM in human glioblastoma cells, both in vivo and in vitro (57)(58)(59). The elevated expression of IL-6 cytokines is thought to be responsible, at least in part, for both constitutive and induced activation of STAT-3 in glioblastoma.…”

“…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).…”

Targeting Stat3 blocks both HIF-1 and VEGF expression induced by multiple oncogenic growth signaling pathways

“…Activation of Stat3 leads to tumor angiogenesis in vivo (Niu et al, 2002b) and blocking Stat3 signaling in tumors can reduce tumor angiogenesis (Wei et al, 2003a, b). A role of Stat3 in upregulating VEGF expression in diverse human cancers has also been demonstrated (Repovic et al, 2003;Wei et al, 2003a, b). Importantly, constitutive activation of Stat3 occurs at 50-90% frequency in a broad range of human cancers (Grandis et al, 1998;Catlett-Falcone et al, 1999;Darnell, 2002;Niu et al, 2002a;Yu and Jove, 2004), suggesting that Stat3 activity contributes significantly to tumor VEGF overproduction.…”

Vascular Endothelial Growth Factor Is Induced by the Inflammatory Cytokines Interleukin-6 and Oncostatin M in Human Adipose Tissue In Vitro and in Murine Adipose Tissue In Vivo

“…21 Combined treatment with OSM and IL-1␤ has been shown to synergistically upregulate VEGF release in astroglioma cells and smooth muscle cells. 17,18 Visceral and subcutaneous preadipocytes, adipocytes, and adipose tissue explants were stimulated with OSM (100 or 10 ng/mL) and IL-1␤ (1 ng/mL) for 48 hours. IL-1␤ enhanced significantly OSM-induced VEGF secretion in all cell and tissue types (Figure 2A through 2F).…”