Chronic pepsin exposure promotes anchorage-independent growth and migration of a hypopharyngeal squamous cell line. Otolaryngol Head Neck Surg 2014 Apr;150(4):618-24
Date
01/01/2014Pubmed ID
24376122Pubmed Central ID
PMC4423599DOI
10.1177/0194599813517862Scopus ID
2-s2.0-84899057392 (requires institutional sign-in at Scopus site) 37 CitationsAbstract
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.
Author List
Kelly EA, Samuels TL, Johnston NAuthor
Nikki Johnston PhD Professor in the Otolaryngology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ApoptosisCarcinogenesis
Carcinoma, Squamous Cell
Cell Movement
Dose-Response Relationship, Drug
Gastroesophageal Reflux
Humans
Hypopharyngeal Neoplasms
Hypopharynx
Pepsin A
Reference Values
Sensitivity and Specificity
Tumor Cells, Cultured