Chronic pepsin exposure promotes anchorage-independent growth and migration of a hypopharyngeal squamous cell line

Elizabeth A. Kelly, Tina L. Samuels, Nikki Johnston

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


Outcome Objectives. (1) Investigate the role of reflux, specifically pepsin, in laryngopharyngeal carcinogenesis. (2) Evaluate effects of chronic pepsin exposure on cell migration, apoptosis, and colony-forming ability in hypopharyngeal cells. Study Design. Translation research. Setting. Academic research laboratory. Methods. Human hypopharyngeal squamous carcinoma FaDu cells were chronically exposed to nonacidic pepsin (exposed for 24 hours, 4 times over 2 weeks at the following concentrations: 0.01 mg/mL, 0.1 mg/mL, or 1 mg/mL). Precise wounds were created in confluent cell plates, and rates of cell migration into wounds were quantified. Separately, cell viability of chronic pepsin-exposed FaDu cells acutely treated with paclitaxel was measured. Finally, a clonogenic assay was performed on these cells to measure effects of chronic pepsin exposure on colony-forming ability. Results. An increased rate of relative wound density was observed in chronic pepsin-treated (0.01 mg/mL, 0.1 mg/ mL) cells compared with control (P < .001), suggesting greater rates of cell migration. Pepsin-treated (0.1 mg/mL) cells demonstrated on average greater cell viability compared with control after exposure to paclitaxel, suggesting possible apoptotic resistance; however, this was not statistically significant. Chronic pepsin exposure (0.1 mg/mL, 1 mg/ mL) was associated with a dose-dependent increase in colony-forming ability relative to control (P<.001). Conclusion. Hypopharyngeal squamous cell line chronically exposed to pepsin demonstrated increased cell migration and colony-forming ability relative to control cells. These experiments indicate that chronic pepsin exposure acts as a promoter of tumorigenesis and metastasis of airway epithelium, suggesting a role for pepsin in laryngopharyngeal carcinogenesis attributed to gastric reflux.

Original languageEnglish (US)
Pages (from-to)618-624
Number of pages7
JournalOtolaryngology - Head and Neck Surgery (United States)
Issue number4
StatePublished - Apr 2014
Externally publishedYes

Bibliographical note

Funding Information:
Funding source: Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, provided financial support for the research study. Grant 1UL1RR031973 from the clinical and translational Science Award program of the National Center for Research Resources, National Institutes of Health, provided statistical support and interpretation of the data.


  • laryngeal cancer
  • laryngopharyngeal reflux
  • pepsin
  • reflux


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