Search

Effect of verapamil treatment in combination with dose-dependent chemotherapies on gastric cancer cell lines viability.

Detection of cells expressing CD44 and ALDH activity in gastric tumorspheres in vitro.

Detection of ALDH+ population with SP protocol and with ALDEFLUOR protocol.

Supplementary experimental procedures,figure legends and references

Background & Aims Studies in animal models have shown that bone marrow−derived cells (BMDC) could be involved in the formation of carcinomas of the upper gastrointestinal tract, including gastric carcinoma. Most gastric carcinomas in humans have been associated with chronic infection with Helicobacter pylori ; we investigated the bacteria's potential to induce premalignant lesions in mice and studied the kinetics of BMDC settlement in the gastric epithelium. Methods C57BL/6J female chimeric mice with BMDCs from male donors that express green fluorescent protein were infected with human-derived and mouse-adapted strains of H pylori and followed. We assessed development of pathologic features and recruitment of BMDC to the gastric mucosa using immunohistochemistry and fluorescent in situ hybridization analyses of gastric tissue sections. Results Infection of mice with different strains of H pylori led to the development of chronic inflammation, hyperplasia, and mucinous metaplasia, and, later in life, of pseudointestinal metaplasia and dysplasia. After 1 year, gastric glands that contained green fluorescent protein−positive male cells were detected in 50%−90% of female chimeric mice infected with H pylori strains; the presence of these glands correlated with the development of pseudointestinal metaplasia. Twenty-two percent of H pylori −induced dysplastic lesions were composed of glands that contained epithelial BMDCs. Conclusions H pylori infection leads to development of chronic inflammation, hyperplasia, metaplasia, and dysplasia, as well as the recruitment and accumulation of BMDC in the gastric epithelial mucosa. Nearly 25% of dysplastic lesions include cells that originate from the BM.