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Increased expression of IL17A in human gastric cancer and its potential roles in gastric carcinogenesis

机译:IL17A在人胃癌中的表达增加及其在胃癌发生中的潜在作用

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摘要

Inflammatory cytokines modulate immune responses in the tumor microenvironment during progression. The role of interleukin (IL) 17A in cancer is currently under debate. We aim to investigate the expression of IL17A in situ tumors as well as in nontumor gastric mucosa tissues and further explore the functional significance of IL17A on gastric cancer cells in vitro. We found that compared with nontumor regions, the expression of IL17A were increased significantly in tumors of gastric cancer patients (P=0.007). The immunoreactivity for IL17A was found only in cytoplasm of inflammatory cells as well as vascular endothelial cells but not in tumor cells. Consistently, IL17A transcription was silenced in a variety of gastric cancer cell lines. In vitro, recombinant human IL17A protein promotes cell proliferation and monolayer wound healing of both AGS and SGC7901cells, in a dose-dependent manner. Besides, IL17A inhibits H2O2-induced cell apoptosis. Expression of IL6 and MMP13 mRNA was increased significantly after IL17A stimulation. These data suggest that accumulation of intratumoral IL17A-producing cells may promote gastric cancer progression directly or by inducing key signal transduction pathways implicated in gastric carcinogenesis.
机译:在进展过程中,炎性细胞因子调节肿瘤微环境中的免疫反应。白细胞介素(IL)17A在癌症中的作用目前正在争论中。我们旨在研究IL17A在原位肿瘤以及非肿瘤胃黏膜组织中的表达,并进一步探讨IL17A在体外对胃癌细胞的功能意义。我们发现,与非肿瘤区域相比,胃癌患者肿瘤中IL17A的表达显着增加(P = 0.007)。对IL17A的免疫反应性仅在炎性细胞以及血管内皮细胞的细胞质中发现,而在肿瘤细胞中未发现。一致地,IL17A转录在多种胃癌细胞系中沉默。在体外,重组人IL17A蛋白以剂量依赖的方式促进AGS和SGC7901细胞的细胞增殖和单层伤口愈合。此外,IL17A抑制H2O2诱导的细胞凋亡。 IL17A刺激后,IL6和MMP13 mRNA的表达显着增加。这些数据表明,肿瘤内产生IL17A的细胞的积累可以直接或通过诱导与胃癌发生有关的关键信号转导途径促进胃癌的进展。

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