Bile acid at low pH reduces squamous differentiation and activates EGFR signaling in esophageal squamous cells in 3-D culture.
BACKGROUND
Barrett's esophagus is a preneoplastic metaplasia in which the normal squamous epithelium of the esophagus changes to an intestinal, columnar phenotype due to long-term gastro-esophageal reflux. The major components of this reflux are bile and stomach acid. Previous in vitro studies on the effect of bile and acid on esophageal cells have predominantly relied on transformed esophageal squamous cells or cancer cells grown in monolayer culture.


CONCLUSIONS
In this study, we expanded our previous work using an immortalized primary esophageal squamous cell line (EPC1). We demonstrate that EPC1 cells form a multi-layer, stratified epithelium when grown on polyester transwell filters in media supplemented with calcium. When exposed to short pulses of bile and pH 5, but not either condition alone, EPC1 cells demonstrate a reduction in stratification layers and reduced expression of squamous epithelium-specific genes. Bile at pH 5 also causes activation of epidermal growth factor receptor and down-stream pathways. Blocking epidermal growth factor receptor activation partially attenuates the effects of bile acid and pH 5. These results suggest that bile at low pH, but not bile or low pH alone, promotes loss of differentiation status of stratified squamous esophageal epithelium in vitro, possibly by initiating a mucosal repair response through epidermal growth factor activation.
Department of Biology, University of Rochester, Rochester, NY, USA.
Sayak
S
Ghatak
Marie
M
Reveiller
Liana
L
Toia
Andrei
A
Ivanov
Tony E
TE
Godfrey
Jeffrey H
JH
Peters
D001647:Bile Acids and Salts / Q000494:pharmacology*; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology*; D004848:Epithelium / Q000473:pathology; D066246:ErbB Receptors / Q000502:physiology*; D004947:Esophagus / Q000473:pathology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D001647:Bile Acids and Salts; C512478:EGFR protein, human; D066246:ErbB Receptors