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Liu et al. J Cancer Metastasis Treat 2017;3:169-76                                  Journal of
           DOI: 10.20517/2394-4722.2017.46
                                                             Cancer Metastasis and Treatment

                                                                                               www.jcmtjournal.com
            Original Article                                                                    Open Access


           The synergy of Helicobacter pylori and lipid

           metabolic disorders in induction of Th17-related

           cytokines in human gastric cancer



           Jie Liu , Han Wang , Gang Chen , Mo Yang , Zhi-Xian Wu , Russell Erick Ericksen , Alice Sze Tsai Wong ,
                                                                                  4
                                                            1,3
                                                                                                     5
                           1
                                                1
                                       2
                 1
           Weiping Han , Jin-Zhang Zeng 1
                      4
           1 Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical
           Sciences, Xiamen University, Xiamen 361102, Fujian, China.
           2 Department of Pathology, Fujian Provincial Cancer Hospital, Fujian Medical University, Fuzhou 350014, Fujian, China.
           3 Department of Hepatobiliary Disease, Fuzhou General Hospital (Dongfang Hospital), Xiamen University, Fuzhou 350025, Fujian, China.
           4 Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore 138667, Singapore.
           5 School of Biological Sciences, University of Hong Kong, Hong Kong 999077, China.
           Correspondence to: Dr. Jin-Zhang Zeng, Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of
           Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, Fujian, China. E-mail: jzzeng@xmu.edu.cn;
           Dr. Weiping Han, Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, Agency for Science, Technology and Research,
           Singapore 138667, Singapore. E-mail: Weiping_Han@sbic.a-star.edu.sg
           How to cite this article: Liu J, Wang H, Chen G, Yang M, Wu ZX, Ericksen RE, Wong AST, Han W, Zeng JZ. The synergy of Helicobacter pylori
           and lipid metabolic disorders in induction of Th17-related cytokines in human gastric cancer. J Cancer Metastasis Treat 2017;3:169-76.
                                         ABSTRACT

            Article history:              Aim: To study the impact of Helicobacter pylori (H. pylori) and lipid metabolic disorder
            Received: 03-07-2017          on the expression of Th17-related cytokines in gastric cancer (GC).  Methods: GC
            Accepted: 22-08-2017          specimens were randomly collected from 42 patients, of whom 15 had H. pylori infection
            Published: 29-08-2017         and 27 were without. Tumor RNA was extracted for reverse transcription quantitative
                                          polymerase chain reaction quantification of gene expression. Results: The mRNA levels
            Key words:                    of interleukin (IL)-6 and leptin, which are known to regulate Th17 differentiation, were
            Helicobacter pylori,          upregulated by 20 and 6 folds, respectively, in H. pylori-infected compared to uninfected
            T helper cells,               patients. IL-17A and granulocyte-macrophage colony-stimulating factor, two cytokines
            gastric cancer,               produced by Th17 cells, were 5- and 6-fold higher in tumors with H. pylori infection,
            interleukin-17A,              respectively. Consistently, RORγt, a transcription factor regulating Th17 differentiation,
            RORγt                         was increased 6-fold in H. pylori-positive vs. negative tumors. Further elevation of RORγt

                                          was seen in advanced H. pylori-associated tumors. In addition, H. pylori infection was
                                          also associated with enhanced expression of CXCL1 (5 folds), chemotactic factor capable
                                          of driving bone marrow-derived immature myeloid cells. Interestingly, we observed that
                                          H. pylori-associated increase of IL-17A was enhanced in the group with higher plasma
                                          triglycerides. Conclusion: The findings demonstrate a cross-talk and synergistic role of
                                          H. pylori infection and abnormal lipid metabolism in GC development, at least partly via
                                          cooperative induction of Th17 differentiation and activation.


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