Document Detail

Pepsin promotes proliferation of laryngeal and pharyngeal epithelial cells.
MedLine Citation:
PMID:  22570308     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE/HYPOTHESIS: 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.
STUDY DESIGN: Translational research study.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: These data support a role for refluxed pepsin in the promotion of epithelial proliferation and carcinogenesis of the larynx and pharynx.
Nikki Johnston; Justin C Yan; Craig R Hoekzema; Tina L Samuels; Gary D Stoner; Joel H Blumin; Jonathan M Bock
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-05-08
Journal Detail:
Title:  The Laryngoscope     Volume:  122     ISSN:  1531-4995     ISO Abbreviation:  Laryngoscope     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-07     Completed Date:  2012-08-17     Revised Date:  2013-11-07    
Medline Journal Info:
Nlm Unique ID:  8607378     Medline TA:  Laryngoscope     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1317-25     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.
Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
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MeSH Terms
Biopsy, Needle
Blotting, Western
Case-Control Studies
Cell Proliferation / drug effects*
Cells, Cultured
Epithelial Cells / cytology,  drug effects*
Flow Cytometry
Fluorescent Antibody Technique
Hypopharynx / cytology*,  drug effects
Laryngeal Neoplasms / pathology*
MicroRNAs / analysis
Microarray Analysis
Pepsin A / pharmacology*
Polymerase Chain Reaction / methods
Reference Values
Sensitivity and Specificity
Grant Support
Reg. No./Substance:
0/MicroRNAs; EC A

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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