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Pepsin promotes proliferation of laryngeal and pharyngeal epithelial cells. Laryngoscope 2012 Jun;122(6):1317-25

Date

05/10/2012

Pubmed ID

22570308

Pubmed Central ID

PMC3816638

DOI

10.1002/lary.23307

Scopus ID

2-s2.0-84861808837   54 Citations

Abstract

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.

Author List

Johnston N, Yan JC, Hoekzema CR, Samuels TL, Stoner GD, Blumin JH, Bock JM

Authors

Joel H. Blumin MD Chief, Professor in the Otolaryngology department at Medical College of Wisconsin
Jonathan Bock MD Associate Professor in the Otolaryngology 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

Biopsy, Needle
Blotting, Western
Case-Control Studies
Cell Proliferation
Cells, Cultured
Epithelial Cells
Female
Flow Cytometry
Fluorescent Antibody Technique
Humans
Hypopharynx
Laryngeal Neoplasms
Male
MicroRNAs
Microarray Analysis
Pepsin A
Polymerase Chain Reaction
Reference Values
Sensitivity and Specificity
jenkins-FCD Prod-480 9a4deaf152b0b06dd18151814fff2e18f6c05280