This research study was sponsored by the Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, U.S.A. The authors have no other funding, financial relationships, or conflicts of interest to disclose.
Pepsin promotes proliferation of laryngeal and pharyngeal epithelial cells†
Version of Record online: 8 MAY 2012
Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.
Volume 122, Issue 6, pages 1317–1325, June 2012
How to Cite
Johnston, N., Yan, J. C., Hoekzema, C. R., Samuels, T. L., Stoner, G. D., Blumin, J. H. and Bock, J. M. (2012), Pepsin promotes proliferation of laryngeal and pharyngeal epithelial cells. The Laryngoscope, 122: 1317–1325. doi: 10.1002/lary.23307
- Issue online: 1 JUN 2012
- Version of Record online: 8 MAY 2012
- Accepted manuscript online: 22 MAR 2012 10:18AM EST
- Manuscript Accepted: 24 FEB 2012
- Manuscript Revised: 3 JAN 2012
- Manuscript Received: 14 DEC 2011
- laryngopharyngeal reflux;
- squamous cell carcinoma
Laryngopharyngeal reflux (LPR) is thought to be a significant risk factor for laryngeal squamous cell carcinoma (SCC), but causality has never been proven. It is accepted that chronic reflux into the esophagus can induce metaplastic changes in esophageal mucosa with subsequent increased risk of esophageal adenocarcinoma, but no similar associations have been established for LPR and laryngopharyngeal SCC. The objective of this study was to test the hypothesis that reflux of pepsin into the laryngopharynx can promote carcinogenesis.
Translational research study.
Normal human laryngeal primary epithelial cell cultures and hypopharyngeal FaDu SCC cells were exposed to human pepsin and analyzed by Human Cancer PathwayFinder and miRNA Superarrays, flow cytometry, and Western blot to determine the effect of pepsin on carcinogenesis. Laryngeal biopsy specimens taken from cancer patients and normal control subjects were analyzed for the presence of pepsin by Western blot.
Microarray analysis demonstrated that pepsin significantly altered the expression of 27 genes implicated in carcinogenesis and also affected the expression of 22 microRNAs known to be altered in human head and neck cancers. Pepsin increased proliferation in both FaDu SCC cells and cultured normal laryngeal epithelial primary cells by increasing S phase distribution on flow cytometry analysis in a time- and dose-dependent manner. Furthermore, pepsin was detected in 60% (3/5) human laryngeal cancer biopsies, absent in all (0/5) normal control specimens.
These data support a role for refluxed pepsin in the promotion of epithelial proliferation and carcinogenesis of the larynx and pharynx. Laryngoscope, 2012