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Clin Cancer Res. 2008 May 15;14(10):2909-17. doi: 10.1158/1078-0432.CCR-07-4467.

Helicobacter pylori augments growth of gastric cancers via the lipopolysaccharide-toll-like receptor 4 pathway whereas its lipopolysaccharide attenuates antitumor activities of human mononuclear cells.

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  • 1Department of Surgery, National Defense Medical College, Namiki, Tokorozawa, Japan. grd1705@ndmc.ac.jp

Abstract

PURPOSE:

Helicobacter pylori is reportedly involved in the development of gastric cancer. We investigated the mechanisms by which H. pylori affects gastric cancer growth and antitumor immunities in the host, focusing on H. pylori-derived lipopolysaccharide (LPS).

EXPERIMENTAL DESIGN:

H. pylori and four gastric cancer cell lines (MKN28, MKN45, NUGC3, and KATOIII) were used. We examined the effect of H. pylori or its LPS stimulation on cancer growth and the involvement of the H. pylori LPS-toll-like receptor 4 (TLR4) pathway. We also examined the cytotoxicities of H. pylori/LPS-stimulated human mononuclear cells (MNC) against gastric cancer cells and the effect of H. pylori LPS stimulation on cytokine production by MNC.

RESULTS:

H. pylori, as well as its LPS, augmented the growth of gastric cancers, all of which expressed TLR4. Neutralization of TLR4 almost completely abrogated the H. pylori-induced proliferative activity of cancer cells. Escherichia coli LPS also augmented cancer growth via the LPS-TLR4 pathway. However, only H. pylori-derived LPS attenuated the cytotoxicity of MNC against gastric cancer cells. Stimulation with H. pylori/LPS also down-regulated perforin production in cancer cell-cocultured CD56+ natural killer cells. H. pylori LPS induced neither interleukin-12 nor IFN-gamma production by MNC, although E. coli LPS did induce production of both significantly. Nevertheless, interleukin-12 stimulation restored the IFN-gamma-producing capacity of H. pylori LPS-stimulated MNC.

CONCLUSION:

H. pylori augmented the growth of gastric cancers via the LPS-TLR4 pathway, whereas it attenuated the antitumor activity and IFN-gamma-mediated cellular immunity of MNC. H. pylori infection might thereby promote proliferation and progression of gastric cancers.

PMID:
18483357
[PubMed - indexed for MEDLINE]
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