Involvement of CCN1 in esophageal malignancy

Background Esophageal adenocarcinoma (EAC) has been the fastest growing cancer in the world. Due to its association with the proliferation of obesity, gastroesophageal reflux disease (GERD) becomes the leading cause for this rise. The causal pathway is likely from normal to GERD to esophagitis to Barrett's esophagus (BE) to EAC. As a matricellular protein, CCN1 up‐regulation has been reported in BE and in normal esophageal epithelial cells under acidic condition. The aim of this study is to examine CCN1 expression and function during esophageal malignancy. Methods For in vivo study, GERD was surgically induced in rats by anastomosing the duodenum to the gastroesophageal junction. For in vitro study, normal human esophageal epithelial cells (Het‐1A) were treated with bile salt cocktail at pH 7.0 or 5.5. Human EAC cells (OE19 and OE33) and tissue array were used to assess CCN1 levels at the malignant stage. Results (1) CCN1 was highly up‐regulated in Het‐1A cells by bile acid but declined as the condition continued. (2) GERD rats developed severe esophagitis within 4 weeks after surgery, accompanied by the soar of CCN1, which declined as GERD continued. (3) CCN1 level was found lower in both OE19 and OE33 cells than in Het‐1A cells and lower in EAC tumor tissue compared to normal esophageal tissue. Conclusions CCN1 expression during esophageal malignancy follows a pattern: high in GERD, moderate in BE, and low in EAC.