Chronic Pepsin Exposure Promotes Anchorage-Independent Growth and Migration of a Hypopharyngeal Squamous Cell Line. (April 2014)

• Record Type: Journal Article
• Authors: Kelly, Elizabeth A.; Samuels, Tina L.; Johnston, Nikki
• Is Part Of: Otolaryngology--head and neck surgery. Volume 150:Number 4(2014:Apr.)
• Page Start: 618
• Page End: 624
• Publication Date: 2014-04
• Subjects: pepsin -- laryngopharyngeal reflux -- laryngeal cancer -- reflux; Head -- Surgery -- Periodicals; Neck -- Surgery -- Periodicals; Otolaryngology -- Periodicals; 617.51
• DOI: 10.1177/0194599813517862
• Languages: English
• ISSNs: 0194-5998

Abstract

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.