Increased expression of IL17A in human gastric cancer and its potential roles in gastric carcinogenesis
Increased expression of IL17A in human gastric cancer and its potential roles in gastric carcinogenesis
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DOI：
10.1007/s13277-014-1697-3
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发表时间：
2014-06-01
期刊：
影响因子：
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通讯作者：
Hu, Pinjin
中科院分区：
文献类型：
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作者：
Wu, Xiaoqin;Zeng, Zhirong;Hu, Pinjin
炎性细胞因子在肿瘤进展过程中调节微环境中的免疫反应。白介素17A在癌症中的作用目前还在争论中。我们的目的是研究IL17A在原位肿瘤和非肿瘤胃粘膜组织中的表达，进一步探讨IL17A在体外培养的胃癌细胞中的功能意义。我们发现，与非肿瘤区域相比，胃癌患者肿瘤组织中IL17A的表达显著增加(P=0.007)。IL 17A仅见于炎症细胞和血管内皮细胞的胞浆中，而在肿瘤细胞中未见表达。在多种胃癌细胞系中，IL17A的转录一直处于沉默状态。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还可抑制过氧化氢诱导的细胞凋亡。IL-17A刺激后，IL-6和MMP13的mRNA表达显著增加。这些数据表明，肿瘤内产生IL17A的细胞的聚集可能直接或通过诱导与胃癌发生有关的关键信号转导途径来促进胃癌的进展。
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.