Involvement of tumor necrosis factor-alpha in the upregulation of CXCR4 expression in gastric cancer induced by Helicobacter pylori.
Involvement of tumor necrosis factor-alpha in the upregulation of CXCR4 expression in gastric cancer induced by Helicobacter pylori.
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DOI：
10.1186/1471-2407-10-419
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发表时间：
2010-08-11
期刊：
影响因子：
3.8
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Zhao C;Lu X;Bu X;Zhang N;Wang W
幽门螺杆菌的感染会增加肿瘤的侵袭和转移，通常被认为是胃癌发展的最强危险因素。 CXCR4 的过度表达并明显参与胃癌转移似乎并非巧合。本研究的目的是试图调查并进一步建立它们之间的联系。由于H. pylori是TNF-α的强效诱导剂，肿瘤促进剂TNF-α是否参与H. pylori诱导CXCR4表达也是本研究的研究对象。通过实时PCR测定CXCR4、TNF-α、IL-6和IL-1β mRNA的表达。通过Western blotting检测CXCR4蛋白表达。使用 Quantikine Elisa 试剂盒测量细胞培养上清液中 TNF-α、IL-6 和 IL-1β 的浓度。为了消除HGC27细胞中TNF-α的表达，使用TNF-α RNAi质粒转染它们。与幽门螺杆菌阴性胃癌 (n = 15) 相比，幽门螺杆菌阳性胃癌 (n = 19) 的 CXCR4 和 TNF-α mRNA 水平显着较高。随后的Spearman等级相关检验显示，34例原发性胃癌中CXCR4 mRNA水平与TNF-α水平呈正相关。其他结果如下：胃癌细胞MKN45和HGC27感染H. pylori 26695（cag PAI+）或Tx30a（cag PAI-）后CXCR4和TNF-α表达上调；幽门螺杆菌对 CXCR4 表达的诱导可被中和 TNF-α 抗体英夫利昔单抗显着抑制；外源TNF-α处理或与巨噬细胞共培养后，MKN45细胞中CXCR4表达上调；转染TNF-α RNAi质粒后，HGC27细胞中CXCR4表达下调。用幽门螺杆菌 26695 处理的 MKN45 细胞的迁移显着增加，而当添加 CXCR4 拮抗剂 AMD 3100 或英夫利昔单抗时，其迁移受到强烈抑制。我们的研究结果表明，幽门螺杆菌通过 TNF-α 上调胃癌中 CXCR4 的表达。
H. pylori, whose infection increases tumor invasiveness and metastasis, is generally labelled as the strongest risk factor for the development of gastric cancer. It appears not to be a coincidence that there is also an overexpression of CXCR4 and an obvious involvement in gastric cancer metastasis. The aim of this study attempts to investigate and further to establish a link between them. With H. pylori being a potent inducer of TNF-α, whether TNF-α, a tumor promoter, is involved in the induction of CXCR4 expression by H. pylori was also under research in this study. Expression of CXCR4, TNF-α, IL-6 and IL-1β mRNA was determined by real-time PCR. CXCR4 protein expression was detected by Western blotting. Concentrations of TNF-α, IL-6 and IL-1β in cell culture supernatants were measured using the Quantikine Elisa kit. To abrogate TNF-α expression in HGC27 cells, TNF-α RNAi plasmid was used to transfect them. Levels of CXCR4 and TNF-α mRNA were significantly higher in H. pylori-positive gastric cancers (n = 19) compared to H. pylori-negative ones (n = 15). A subsequently Spearman's rank correlation test showed there was a positive correlation between the level of CXCR4 mRNA and that of TNF-α in 34 primary gastric cancers. Other results followed: Expression of CXCR4 and TNF-α was upregulated in gastric cancer cell MKN45 and HGC27 after infection with H. pylori 26695 (cag PAI+ ) or Tx30a (cag PAI- ); The induction of CXCR4 expression by H. pylori was inhibited significantly by a neutralizing TNF-α antibody, infliximab; CXCR4 expression was upregulated in MKN45 cells after treatment with exogenous TNF-α or co-culture with macrophage, and was downregulated in HGC27 cells after transfection with TNF-α RNAi plasmid. There was a significant increase in the migration of MKN45 cells treated with H. pylori 26695, and a strong inhibition when AMD 3100, a CXCR4 antagonist, or infliximab, was added. Our findings demonstrated that H. pylori upregulates CXCR4 expression in gastric cancer through TNF-α.
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影响因子：
82.9
作者：
Moore, RJ;Owens, DM;Balkwill, F
通讯作者：
Balkwill, F
影响因子：
4.6
作者：
Schmausser, B;Endrich, S;Eck, M
通讯作者：
Eck, M
影响因子：
6.4
作者：
Sujanuma, Masami;Yamaguchi, Kensei;Fujiki, Hirota
通讯作者：
Fujiki, Hirota
DOI：
10.1084/jem.177.5.1391
发表时间：
1993-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Orosz P;Echtenacher B;Falk W;Rüschoff J;Weber D;Männel DN
通讯作者：
Männel DN
影响因子：
--
作者：
Kwak, MK;Hur, K;Yang, HK
通讯作者：
Yang, HK