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Local Synthesis of Pepsin in Barrett's Esophagus and the Role of Pepsin in Esophageal Adenocarcinoma. Ann Otol Rhinol Laryngol 2015 Nov;124(11):893-902



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Scopus ID

2-s2.0-84952334416   6 Citations


OBJECTIVE: Despite widespread use of proton pump inhibitors (PPIs), the incidence of esophageal adenocarcinoma (EAC) continues to rise. PPIs reduce reflux acidity, but only transiently inactivate gastric enzymes. Nonacid reflux, specifically nonacid pepsin, contributes to carcinogenesis in the larynx. Given the carcinogenic potential of pepsin and inefficacy of PPIs to prevent EAC, the presence and effect of pepsin in the esophagus should be investigated.

METHODS: Normal and Barrett's biopsies from 8 Barrett's esophagus patients were collected for pepsin analysis via Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR). Human esophageal cells cultured from healthy patients were treated with pepsin (0.01-1 mg/mL; 1-20 hours), acid (pH 4)┬▒pepsin (5 minutes); real-time RT-PCR, ELISA, and cell migration were assayed.

RESULTS: Pepsin was detected in all 8 Barrett's and 4 of 8 adjacent normal specimens. Pepsinogen mRNA was observed in 22 Barrett's, but not in normal adjacent samples. Pepsin induced PTSG2 (COX-2) and IL-1╬▓ expression and cell migration in vitro.

CONCLUSIONS: Pepsin is synthesized by metaplastic, Barrett's esophageal mucosa. Nonacid pepsin increases metrics of tumorigenicity in esophageal epithelial cells in vitro. These findings implicate refluxed and locally synthesized pepsin in development and progression of EAC and, in part, explain the inefficacy of PPIs in the prevention of EAC.

Author List

Samuels T, Hoekzema C, Gould J, Goldblatt M, Frelich M, Bosler M, Lee SH, Johnston N


Matthew I. Goldblatt MD Professor in the Surgery department at Medical College of Wisconsin
Jon Gould MD Chief, Professor in the Surgery department at Medical College of Wisconsin
Nikki Johnston PhD Associate Professor in the Otolaryngology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Barrett Esophagus
Cell Migration Assays
Cells, Cultured
Disease Progression
Esophageal Neoplasms
Gastroesophageal Reflux
Pepsin A
Proton Pump Inhibitors
jenkins-FCD Prod-480 9a4deaf152b0b06dd18151814fff2e18f6c05280