Cell recruitment in gastric carcinogenesis

th most common malignant disease and the 3 rd leading cause of cancer death worldwide. Like most cancers, incidence increases with age. Unlike most other cancers a dominant environmental cause has been established, as chronic infection by Helicobacter pylori contributes about 90% of the attributable risk in " non-cardia " gastric cancer, the most common type globally [1]. The development of gastric cancer is a decades-long process, and usually follows an established sequence of progressive histopathological changes from chronic gastritis (occurring soon after H. pylori acquisition in childhood) through glandular atrophy, intestinal metaplasia, dysplasia and invasive cancer. This cascade was first described even before H. pylori was appreciated as the initial stimulus in this process [2]. The mechanisms underlying the contribution of H. pylori to gastric carcinogenesis have been investigated intensely since H. pylori was classified by the WHO as a definite carcinogen in 1994. Increased virulence among H. pylori strains is conferred by carriage of the cytotoxin-associated gene (cag) pathogenicity island, as the cagA gene encodes an oncogenic CagA protein that can be translocated into gastric epithelial cells to promote tumorigenic activity. In an important and provocative publication, Houghton et al provided evidence in a mouse model that bone marrow-derived cells (BMDC) recruited to the gastric mucosa inflamed by chronic Helicobacter infection might become the cells that comprise the resultant gastric dysplasia [3]. Another group has confirmed the incorporation of BMDCs into 25% of the dysplastic gastric glands in mice infected by a murine-adapted Editorial human H. pylori strain [4]. However, the absence of BMDCs in most of the dysplastic gastric lesions [4] and the failure of progression from dysplasia to cancer in most mouse models, indicates the need to consider additional contributory factors, genetic, environmental or age-related, when testing the gastric BMDC-cancer hypothesis. We recently explored the contribution of BMDCs to gastric cancer induced by H. pylori in p27-deficient mice, since in this model H. pylori infection slowly promotes gastric cancer in the mouse equivalent of middle to old age after progressing through the histological intermediaries noted in humans. The goal of our recently published work was to determine whether the loss of p27 expression in bone marrow-derived cells (in a background of wild type epithelium) or loss of p27 expression in gastric epithelial cells (with wild type BM cells) was the cause of the increased gastric cancer susceptibility of these mice [5]. For this purpose, we generated …