Faculty Collaboration Database

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

01/01/2014

Pubmed ID

24376122

Pubmed Central ID

PMC4423599

DOI

10.1177/0194599813517862

Scopus ID

2-s2.0-84899057392   18 Citations

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.

Author List

Kelly EA, Samuels TL, Johnston N

Author

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

Apoptosis
Carcinogenesis
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