Barrett's Esophagus Associated Stem Cells.
Sarah Heaton, Paula Sochacki, Nabiha Khoury, Edi Levi. John D. Dingell VA Medical Center, Detroit, MI; Wayne State University School of Medicine, Detroit
Background: Barrett's esophagus is a squamous to columnar metaplasia that develops as a result of chronic gastroesophageal reflux disease. Barrett's metaplasia is a preneoplastic condition for esophageal adenocarcinoma. A current prevailing hypothesis suggests that cancer is a disease of stem cells or "tumor initiating cells". It would follow that precancerous lesions such as Barrett's esophagus is also a disease of stem cells. Currently, it is unknown where in the normal esophagus the stem cells are located. Popular theory suggests that the stem cells are either within the submucosal glands or the basal cells of the squamous epithelium. Another possibility is that the stem cells are derived from the bone marrow.
Design: In this study, we attempted to locate the stem cells in normal esophagus (n=8), Barrett's esophagus (n=12), Barrett's esophagus with dysplasia (n=4) and esophageal adenocarcinoma (n=24). We used stem cell markers Lgr5, ALDH1, and CD166 for immunohistochemical detection of stem cells in the specimens.
Results: In the normal esophageal mucosa, ALDH1 staining revealed stem cells in the submucosal glands and ducts opening to the lumen of the esophagus. In Barrett's esophagus with or without dysplasia, Lgr5, ALDH1, and CD166 stains revealed stem cells in the base of the crypts of the metaplastic glands and also in submucosal glands. In adenocarcinomas associated with Barrett's, all three markers were expressed in a focal manner, preferentially at the invasive fronts of tumors.
Conclusions: Based on our findings, we believe that the progenitor cells for the Barrett's esophagus are located in the ducts of submucosal glands. Metaplastic glands of Barrett's esophagus harbor stem cells. Gastrointestinal cancers associated with Barrett's do contain stem cells demonstrated by the markers ALDH1, Lgr5, and CD166. Stem cells can be targeted for novel therapies for the prevention of cancers associated with Barrett's.
Monday, February 28, 2011 1:00 PM
Poster Session II # 90, Monday Afternoon