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Gained in translation: the importance of biologically relevant models of Helicobacter pylori-induced gastric cancer
  1. Richard M Peek Jr1,2,
  2. Ernst J Kuipers3,4,5
  1. 1Department of Medicine, Division of Gastroenterology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
  2. 2Department of Cancer Biology, Division of Gastroenterology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
  3. 3Department of Gastroenterology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
  4. 4Department of Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
  5. 5Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands
  1. Correspondence to Dr Richard M Peek, Mina C. Wallace Professor of Medicine and Cancer Biology, Vanderbilt University School of Medicine, 2215B Garland Avenue, 1030C Medical Research Building IV, Nashville, TN 37232-2279, USA; richard.peek{at}vanderbilt.edu

https://doi.org/10.1136/gutjnl-2011-301342

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    The attributable risk of gastric cancer conferred by Helicobacter pylori ranges from 75% to more than 90% depending on H pylori prevalence; however, only a fraction of colonised persons ever develop neoplasia.1 2 Disease risk involves well-choreographed interactions between pathogen and host, which are dependent upon strain-specific bacterial factors as well as host genotypic traits, each of which can be amplified by the environment. In their paper published in Gut, Kwon et al provide fresh insights into the role of a tumour suppressor, vitamin D3 upregulated protein 1 (VDUP1), in H pylori-associated gastric carcinogenesis (see page 53).3 Importantly, these investigators used multiple model systems to demonstrate that VDUP1 negatively regulates carcinogenesis induced by the combination of H pylori and N-methyl-N-nitrosourea (MNU) via dissociating proliferation from apoptosis and suppression of tumour necrosis factor α (TNFα)-dependent nuclear factor κB (NF-κB) activation and subsequent cyclooxygenase-2 (COX-2) expression.

    Using a genetic model of VDUP1 deficiency, Kwon and colleagues observed that the incidence and severity of gastric premalignant and malignant lesions was increased in vdup1−/− mice compared with wild-type mice.3 This was accompanied by hyperproliferation that was not balanced by a corresponding increase in apoptosis. Contact between H pylori and epithelial cells in vitro dysregulates signalling pathways that influence oncogenesis, which mirrors interactions between H pylori and epithelial cells that occur within infected tissue. Kwon et al therefore also used an in vitro …

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    Footnotes

    • Linked article 300361.

    • Funding Supported in part by National Institutes of Health grants DK58587, CA116037 and CA77955.

    • Competing interests None.

    • Provenance and peer review Commissioned; internally peer reviewed.

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