Role of<i>CD14</i>Promoter Polymorphisms in<i>Helicobacter pylori</i>Infection–Related Gastric Carcinoma

Zhao, Dan; Sun, Tong; Zhang, Xuemei; Guo, Yongli; Yu, Dianke; Yang, Ming; Tan, Wen; Wang, Guiqi; Lin, Dong

doi:10.1158/1078-0432.ccr-06-2612

Cited by 40 publications

(45 citation statements)

References 55 publications

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“…Because this is an ongoing molecular epidemiologic study of gastric cancer, a report on part of this case-control panel (both n ¼ 470) was published previously. 10 Among these cSNPs, only the Ala2Asp SNP has a minor allelic frequency >1% in the Chinese population (HapMap data release 21a) and, thus, was selected for genotyping in the current study. Genomic DNA was extracted from peripheral blood lymphocytes in all participants.…”

Section: Individuals For Case-control Analysismentioning

confidence: 99%

Genetic polymorphism in chemokine CCL22 and susceptibility to Helicobacter pylori infection‐related gastric carcinoma

Wang

Tan

et al. 2009

Cancer

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BACKGROUND: Gastric carcinoma is widely considered to be related to Helicobacter pylori infection, and the chemokine (C‐C motif) ligand 22 (CCL22) plays an important role in suppressing immune responses against H. pylori and tumor cells. In this study, the authors examined the association between single nucleotide polymorphisms (SNPs) in the CCL22 gene and the risk of gastric carcinoma. METHODS: Information on SNPs in the CCL22 coding region was obtained from the HapMap Project database. Genotypes were determined in a case‐control cohort that consisted of 1001 patients with gastric carcinoma and 1066 controls, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were computed by using a logistic regression model. Serum H. pylori antibody levels were measured by using an enzyme‐linked immunosorbent assay. RESULTS: The 16C→A SNP (reference SNP no. 4359426) in exon 1 of the CCL22 gene, which causes a 2 aspartate (2Asp) to 2 alanine (2Ala) substitution in the CCL22 protein, was associated with a significantly increased risk of gastric carcinoma. Individuals who were homozygous for the Ala/Ala genotype had an OR of 2.27 (95% CI, 1.28‐4.02) compared with individuals who had the Asp/Asp genotype. Stratification analysis indicated that the association was more pronounced among men (OR, 2.64; 95% CI, 1.29‐5.41) and among younger individuals (OR, 2.85; 95% CI, 1.36‐5.96) compared with women and older individuals. Moreover, a multiplicative joint effect between the CCL22 SNP and H. pylori infection that intensified the risk was observed (OR for the presence of both Ala/Ala genotype and H. pylori infection, 18.37; 95% CI, 2.30‐146.67). CONCLUSIONS: The results from this study suggested that the CCL22 polymorphism is associated with an increase risk of developing H. pylori infection‐related gastric carcinoma. Cancer 2009. © 2009 American Cancer Society.

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Section: Individuals For Case-control Analysismentioning

confidence: 99%

Genetic polymorphism in chemokine CCL22 and susceptibility to Helicobacter pylori infection‐related gastric carcinoma

Wang

Tan

et al. 2009

Cancer

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“…Specifically, membrane CD14, together with TLR4, binds to LPS and transmits signals into the nucleus, activating the release of a series of cytokines (8,9), which may promote gastric carcinogenesis. For example, a previous study found that certain polymorphisms of the CD14 gene promoter region are associated with the susceptibility to gastric cancer, which could be due to alterations in CD14 expression (10).…”

Section: Introductionmentioning

confidence: 99%

CD14 regulates gastric cancer cell epithelial-mesenchymal transition and invasion in vitro

Zhang

et al. 2013

Oncology Reports

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Abstract. Cluster of differentiation 14 (CD14) protein functions as a co-receptor with either the Toll-like receptor TLR4 or MD-2 in the detection of bacterial lipopolysaccharide (LPS) and plays a role in the innate immune system. Recently, it was shown to have effects on the regulation of epithelial-mesenchymal transition (EMT). Thus, the present study investigated the effects of CD14 knockdown on the regulation of gastric cancer cell EMT and invasive capacity following treatment with or without LPS. Knockdown of CD14 expression using CD14 shRNA in MGC-803 cells significantly enhanced E-cadherin expression, but reduced N-cadherin and vimentin expression in both LPS-treated and untreated cells. Morphologically, the phenotype of LPS-treated CD14-knockdown cells was altered to a sporadic long spindle shape. Moreover, TNF-α-treated cells were further elongated, connections between cells were reduced, the gap between the cells was increased and the cells were transformed into mesenchymal cells. Furthermore, the invasive capacity of CD14-knockdown cells was significantly lower compared to that of the negative control shRNA-transfected MGC-803 cells. LPS-treated CD14-knockdown cells had significantly lower levels of tumor cell invasive ability when compared to the LPS-treated parental MGC-803 cells. However, addition of TNF-α to LPS-treated CD14-knockdown cells significantly increased tumor cell invasion. This study demonstrated that CD14 promoted tumor cell EMT and invasion through TNF-α, whereas knockdown of CD14 expression inhibited gastric cancer cell invasion and EMT.

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“…Previous studies have demonstrated that there is a high expression of CD14 and TLR4 in tissues infected with H. pylori, particularly in gastric cancer tissues (14,15). Another study reported that a functional polymorphism of the CD14 promoter was able to affect the expression of CD14 and increase the risk of gastric cancer (16), suggesting that the CD14 protein is important in the transduction of inflam- (17) used LPS to treat A549 non-small cell lung cancer cells and observed that LPS induced tumor cell viability in a time-and dose-dependent manner. However, this effect was inhibited by CD14 and TLR4-neutralizing antibodies.…”

Section: Discussionmentioning

confidence: 99%

CD14 knockdown reduces lipopolysaccharide-induced cell viability and expression of inflammation-associated genes in gastric cancer cells in vitro and in nude mouse xenografts

Zhang

Nie

et al. 2015

Molecular Medicine Reports

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Abstract. The present study examined the role of CD14 in the regulation of lipopolysaccharide (LPS)-induced effects on gastric cancer cells. MGC-803 cells were stably transfected with CD14 short hairpin (sh)RNA and treated with LPS, followed by assessment of cell proliferation, apoptosis and gene expression using a cell counting kit-8 assay, flow cytometry, reverse transcription-polymerase chain reaction and western blot analysis, respectively. The cells subjected to CD14 knockdown were treated with 10 g/ml LPS and injected into nude mice to form tumor xenografts. CD14 shRNA-transfected MGC-803 cells did not exhibit any significant changes in cell viability compared with the control cells (P>0.05), but cell viability was markedly increased in the wild-type (WT) + LPS group (P<0.05). In contrast to the WT + LPS group, the cell viability of the sh-CD14 + LPS group was markedly decreased (P<0.05). In addition, compared with those in the controls, the level of sh-CD14 cell apoptosis did not change significantly; however, it was markedly reduced in the LPS group. Compared with that in the WT + LPS group, the rate of apoptosis in the sh-CD14 + LPS group increased to a certain extent, while it remained lower in the control group. In addition, compared with that in the control, the expression of tumor necrosis factor-α, interleukin (IL)-1, IL-6 and IL-12, and human β-defensin 2 was significantly increased in the WT + LPS group, while, compared with that in the WT + LPS group, the expression of these genes was markedly reduced in the sh-CD14 + LPS group (P<0.05). The nude mouse experiments further confirmed the in vitro data, including the finding that LPS promoted the growth of xenografts, but knockdown of CD14 expression reduced the response of tumor cells to LPS treatment. In conclusion, LPS induced cell viability and the release of inflammatory cytokines, but inhibited gastric cancer cell apoptosis. Knockdown of CD14 expression had no significant effect on gastric cancer malignancy, but mediated LPS signal transduction. IntroductionGastric cancer is one of the most common types of cancer globally and accounted for 989,600 ovel cases and 738,000 cancer-associated fatalities in 2008 (1). >70% of novel gastric cancer cases and fatalities occur in the developing countries, while they have declined in the majority of developed countries, including countries in North America and Europe in previous decades (1). The risk factors for gastric cancer include Helicobacter (H.) pylori infection, history of tobacco smoking, and consumption of smoked foods, salted meat or fish and pickled vegetables. However, intake of fresh fruits and vegetables appears to lower the risk of gastric cancer (1). Regional variations in gastric cancer prevalence reflect the differences in dietary patterns and the prevalence of H. pylori infection (2). H. pylori is an aerobic Gram-negative bacterium found in the stomach, which causes chronic gastritis, peptic ulcers and gastric cancer. Thus, H. pylori infection has been classified as a class I carcinog...

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Role ofCD14Promoter Polymorphisms inHelicobacter pyloriInfection–Related Gastric Carcinoma

Cited by 40 publications

References 55 publications

Genetic polymorphism in chemokine CCL22 and susceptibility to Helicobacter pylori infection‐related gastric carcinoma

Genetic polymorphism in chemokine CCL22 and susceptibility to Helicobacter pylori infection‐related gastric carcinoma

CD14 regulates gastric cancer cell epithelial-mesenchymal transition and invasion in vitro

CD14 knockdown reduces lipopolysaccharide-induced cell viability and expression of inflammation-associated genes in gastric cancer cells in vitro and in nude mouse xenografts

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