(Ivanhoe Newswire)-- Experiments involving mice help provide new insight into what may cause a lethal form of esophageal cancer.
Research linked inflammation and bile acid reflux to the spread of cancer-causing stomach cells into the esophagus. This discovery may help pioneer strategies for treatment.
Esophageal adenocarcinoma is a cancer of the esophagus that is associated with acid reflux disease and Barrett esophagus (BE). BE is characterized by changes in the cells that line the lower esophagus, near the junction with the stomach. In BE, the normal flat esophageal cells are replaced by taller cells resembling those that line the stomach or intestine.
Although many questions about the disease remain unanswered previous research has suggested that BE may be caused by acid reflux disease and chronic inflammation.
"The precise origin of both esophageal adenocarcinoma and BE has been difficult to discern, in part because of the absence of useful experimental model systems that are genetically based," author Dr. Timothy C. Wang, from Columbia University was quoted as saying. "A major unanswered question that has been debated for decades is whether BE cells originate from the lining of the esophagus itself or from the region of the stomach called the cardia that is adjacent to the esophagus.
Dr. Wang and colleagues used a transgenic mouse model of BE and adenocarcinoma that significantly resembles human disease to explore the pathogenesis of the disease. The mice were engineered to express a specific molecule (interleukin-1) associated with chronic esophageal inflammation. The researchers discovered that inflammation and bile acid caused premature cells from the cardia to travel to the esophagus and give rise to the taller "columnar" cells characteristic of BE. Then they identified the exact signaling pathway that appeared to regulate differentiation of the cardia cells into columnar cells, which were associated with the origination of cancer in mice and humans.
The findings suggest that the abnormal cells linked with BE and esophageal adenocarcinoma originate in the cardia of the stomach and not the esophagus. "The fact that BE always begins precisely at the junction where the esophagus meets the stomach has never been explained, and now it seems clear that special consideration should be given to inflammation of the gastric cardia as it may represent a precursor of BE and esophageal adenocarcinoma," Dr. Wang said.
SOURCE: Cancer Cell, January 17, 2012