Authors:
Michael Quante, Govind Bhagat, Julian A. Abrams, Frederic Marache, Pamela Good, Michele D. Lee, Yoomi Lee, Richard Friedman, Samuel Asfaha, Zinaida Dubeykovskaya, Umar Mahmood, Jose-Luiz Figueiredo, Jan Kitajewski, Carrie Shawber, Charles J. Lightdale, Anil K. Rustgi, & Timothy C. Wang
Summary:
Esophageal adenocarcinoma (EAC) arises from Barrett esophagus (BE), intestinal-like columnar metaplasia linked to reflux esophagitis. In a transgenic mouse model of BE, esophageal overexpression of interleukin-1β phenocopies human pathology with evolution of esophagitis, Barrett-like metaplasia and EAC. Histopathology and gene signatures closely resembled human BE, with upregulation of TFF2, Bmp4, Cdx2, Notch1, and IL-6. The development of BE and EAC was accelerated by exposure to bile acids and/or nitrosamines, and inhibited by IL-6 deficiency. Lgr5+ gastric cardia stem cells present in BE were able to lineage trace the early BE lesion. Our data suggest that BE and EAC arise from gastric progenitors due to a tumor-promoting IL-1β-IL-6 signaling cascade and Dll1-dependent Notch signaling.
Source:
Cancer Cell; Vol. 21, Issue 1, 36-51 (01/17/12)