Oncostatin M (OSM) and interleukin-6 (IL-6) are growth factors for prostate cancer (PC). Vascular endothelial growth factor (VEGF) and urokinase-type plasminogen-activator (u-PA) have been implicated in tumour progression. A possible interaction between IL-6, OSM, u-PA and VEGF in PC was investigated.
Primary prostate epithelial cells (PPEC) and DU-145 PC cells were treated with IL-6 or OSM and the effects on u-PA and VEGF expression were studied. Plasma levels of IL-6, OSM, u-PA and VEGF were determined in patients with or without PC.
In DU-145 cells, OSM and IL-6 up-regulated u-PA and VEGF significantly. Higher levels of IL-6 and OSM in metastasising PC than in nonmetastasising PC and benign prostatic hyperplasia (BPH) and correlations between IL-6, OSM, u-PA and VEGF were found.
OSM and IL-6 increase u-PA and VEGF in DU-145 cells but not in PPEC and possibly, by promoting matrix degradation and angiogenesis, could play a role in the pathogenesis of prostate cancer.
"IL-6 is an NF-jB-regulated pleiotropic proinflammatory mediator that signals predominantly via the JAK/ STAT pathway  and enables tumor growth and inhibits apoptosis in a variety of human tumors . A comparison of non-metastazising pancreatic cancer, benign prostatic hyperplasia and metastasized pancreatic cancer revealed elevated levels of IL-6 in the latter, more aggressive tumor . In this study, it was shown that IL-6 leads to an increased expression of urokinase plasminogen activator (uPA) and vascular endothelial growth factor (VEGF), thereby implying a crucial role of IL-6 in angiogenesis of pancreatic tumors. "
[Show abstract][Hide abstract] ABSTRACT: Human pancreatic cancer is one of the most fatal of all solid tissue malignancies. Pancreatic inflammation plays a key role in the development of pancreatic malignancy mediated by pro-inflammatory signalling cascades. Despite advances in surgery and radiation oncology, no significant improvements in overall survival have yet been achieved. Recent investigations suggest a crucial role of interleukin-33 (IL-33), a novel IL-1 family cytokine, in the pathogenesis of chronic pancreatitis and possibly pancreatic cancer. However, the precise role of IL-33 in pancreatic carcinogenesis is poorly understood. As IL-33 mediates its effects via the heterodimeric ST2L/IL-1 receptor accessory protein (IL-1RAcP) receptor complex, we investigated the influence of IL-33 alone, IL-33 combined with IL-1 and other inflammatory cytokines on IL-33 receptor/ligand mRNA expression and production of tumorigenic factors in the highly metastatic human pancreatic adenocarcinoma cell line Colo357. Our results demonstrated that IL-1 and IL-3 up-regulated IL-33 mRNA while IL-12 showed the opposite effect. We also detected a counter-regulatory effect of IL-33 and IL-1 on the mRNA expression of soluble IL-33 receptor ST2 and membrane-bound receptor ST2L. Furthermore, IL-33 and IL-1 acted synergistically in up-regulating secretion of pro-inflammatory IL-6. IL-33 alone stimulated spontaneous release of pro-angiogenic IL-8, but it did not affect IL-1-induced IL-8 secretion. IL-33/IL-1 effects on cytokine production appear to be mediated via NF-κB activation. These data argue for the pro-inflammatory role of IL-33 in Colo357 cells implying that IL-33 might act as a crucial mediator in inflammation-associated pancreatic carcinogenesis.
"These growth factors are glycosylated signaling mitogens that specifically act on endothelial cells and have various effects, including mediating increased vascular permeability, inducing angiogenesis , vasculogenesis and endothelial cell growth, promoting cell migration, and inhibiting apoptosis as well as cell survival functions . Recently, was found interaction between VEGF, IL-6, u-PA and oncostatin M in prostate cancer which is possible important for tumor neovascularization and growth . Moreover, it was shown that VEGFC differentially regulates VEGFA expression in ocular and cancer cells and promotes angiogenesis via RhoA mediated pathway . "
[Show abstract][Hide abstract] ABSTRACT: The expression of different vascular endothelial growth factor (VEGF) genes was studied in glioma U87 cells with endoplasmic reticulum-nuclei-1 (ERN1) loss of function and its regulation by hypoxia and glutamine or glucose deprivation conditions as model of ischemia. The blockade of function of the ERN1 enzyme, which is a major sensor of endoplasmic re-ticulum stress, leads to a decrease of the VEGFA, VEGFB and VEGFC mRNA expression level. The level of VEGFA proteins also decreases at this ex-perimental condition in the cytosolic fraction, but increases in the nuclear fraction. Hypoxia does not affect VEGFC and increases the expression level of VEGFA and VEGFB mRNA in both used cell types, however, the change was much less profound in cells with suppressed function of ERN1. The expression level of VEGFC mRNA decreases in both used cell types in glutamine deprivation condition, however, the change was more profound in control glioma cells. At the same time, the expression level of VEGFA mRNA increases and VEGFB—decreases in gluta-mine deprivation condition in control glioma cells only. Exposure of glioma cells to glucose deprivation condition increases VEGFB mRNA expression level in both used cell types; however, VEGFA—in control glioma cells only and VEGFC—in cells with ERN1 signaling enzyme loss of function only. Thus, the re-sults of this study clearly demonstrated the down-regulation of the expression of all three VEGF genes in glioma cells with ERN1 loss of function which cor-relates to the suppressed angiogenesis and prolifera-tion rate of these cells. Moreover, the effect of hy-poxia and glutamine or glucose deprivation condition on the expression level of all VEGF genes is different and mainly depends on ERN1 signaling enzyme func-tion.
Advances in Biological Chemistry 01/2012; 02(02). DOI:10.4236/abc.2012.22024
[Show abstract][Hide abstract] ABSTRACT: Chronic inflammatory mediators exert pleiotropic effects in the development of cancer. On the one hand, inflammation favors carcinogenesis, malignant transformation, tumor growth, invasion, and metastatic spread; on the other hand inflammation can stimulate immune effector mechanisms that might limit tumor growth. The link between cancer and inflammation depends on intrinsic and extrinsic pathways. Both pathways result in the activation of transcription factors such as NF-κB, STAT-3, and HIF-1 and in accumulation of tumorigenic factors in tumor and microenvironment. STAT-3 and NF-κB interact at multiple levels and thereby boost tumor-associated inflammation which can suppress anti-tumor immune responses. These factors also promote tumor growth, progression, and metastatic spread. IL-1, IL-6, TNF, and PGHS-2 are key mediators of an inflammatory milieu by modulating the expression of tumor-promoting factors. In this review we concentrate on the crucial role of pro-inflammatory mediators in inflammation-driven carcinogenesis and outline molecular mechanisms of IL-1 signaling in tumors. In addition, we elucidate the dual roles of stress proteins as danger signals in the development of anti-cancer immunity and anti-apoptotic functions.
Frontiers in Immunology 01/2011; 2:98. DOI:10.3389/fimmu.2011.00098
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