IL-6 secreted by cancer-associated fibroblasts promotes epithelial-mesenchymal transition and metastasis of gastric cancer via JAK2/STAT3 signaling pathway.
IL-6 was the most increased in the medium of in vitro co-culture of macrophages and GC, and IL-6 elevation was also observed in the peritoneal washes with peritoneal dissemination.
Among the inflammatory cytokines, messages for IL-6, IL-8 and transforming growth factor-beta 1 were produced by gastric cancer (MKN45) cells in response to exposure to the cytotoxic strain of H. pylori.
Associations between polymorphisms in cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)/mannose-binding lectin (MBL)/interleukin-4 (IL-4)/interleukin-6 (IL-6)/phospholipase C ε-1 (PLCE1) and gastric cancer (GC) were already reported by many studies, yet the conclusions of these studies were somehow controversial.
Clinical data revealed that IL-6 was prominently expressed in the stromal portion of GC tissues, and IL-6 upregulation in GC tissues was correlated with poor responsiveness to chemotherapy.
GMF isolated from human gastric cancer and H. pylori infected tissues co-cultured with CD4(+) T cells induced substantially higher levels of Th17 than GMF from normal tissues in an IL-6, TGF-β, and IL-21 dependent manner.
IL-4-590 and IL-6-572 for gastric cancer, and IL-4-590, IL-6-572 and IL-8-251 for peptic ulcer) have a more potent influence on development of gastroduodenal diseases in Western than East Asian populations.
Imbalanced IL-6 family cytokine signalling in the gp130(757FF) mouse model of gastric cancer arising from hyperactivation of oncogenic STAT3 after altered SHP-2 : ERK1/2 signalling produces dysplastic antral tumours preceded by gastritis and metaplasia.
In conclusion, our data indicate that IL-6 induces M2 macrophage differentiation (IL-10<sup>high</sup>TGF-β<sup>high</sup>IL-12 <sub>p35</sub><sup>low</sup> ) by activating STAT3 phosphorylation, and the IL-6-induced M2 macrophages exert a pro-tumor function by promoting GC cell proliferation and migration.
In conclusion, these results indicate that Interleukin-6 promotes tumor growth and metastasis in gastric cancer, resveratrol has the potential to prevent the Interleukin-6 induced gastric cancer metastasis by blocking the Raf/MAPK signaling activation.
In conclusion, we found no correlations between any of the three polymorphisms in the IL-6 gene analyzed in this study and a higher risk of gastritis or gastric cancer.
In short, this study suggested that IL-6R rs2228145 and IL-6rs10499563 genotype were associated with decreased risk of gastric cancer for the individuals with negative and positive Helicobacter pylori infection.
Our study showed that tumor-promoting GC-MSCs contribute to M2 macrophage polarization within the gastric cancer niche through considerable secretion of IL-6 and IL-8.
Recently, the roles of interleukin-6 (IL-6), IL-8 and IL-10 gene polymorphisms in gastric cancer have been extensively studied, with conflicting results.
Single nucleotide polymorphisms of proinflammatory cytokine genes encoding for interleukin 1B (IL1B), IL6, and IL8 have been demonstrated to be associated with an increased risk of gastric cancer.
The combined analysis of IL-6 rs2069837G and JAK1 rs2230587A variant risk genotypes revealed that individuals with one-or-two risk genotypes exhibited an increased risk for GCa (adjusted OR = 1.34; 95% CI = 1.13-1.59).