H+/K+ATPase Expression in the Larynx of Laryngopharyngeal Reflux and Laryngeal Cancer Patients

• Published in: The Laryngoscope 2021-01, Vol.131 (1), p.130-135
• Main Authors: McCormick, Caroline A., Samuels, Tina L., Battle, Michele A., Frolkis, Talia, Blumin, Joel H., Bock, Jonathan M., Wells, Clive, Yan, Ke, Altman, Kenneth W., Johnston, Nikki
• Format: Article
• Language: English
• Subjects: Cells, Cultured; Gastric H+/K+ ATPase; Gene Expression Regulation; H(+)-K(+)-Exchanging ATPase - biosynthesis; H(+)-K(+)-Exchanging ATPase - genetics; Humans; Hypopharynx - cytology; laryngeal cancer; Laryngeal Neoplasms - enzymology; Laryngeal Neoplasms - genetics; Laryngopharyngeal Reflux - enzymology; Laryngopharyngeal Reflux - genetics; Larynx - enzymology; Tumor Cells, Cultured
• ISSN: 0023-852X; 1531-4995
• DOI: 10.1002/lary.28643

Objectives The gastric H+/K+ ATPase proton pump has previously been shown to be expressed in the human larynx, however its contribution to laryngopharyngeal reflux (LPR) signs, symptoms and associated diseases such as laryngeal cancer is unknown. Proton pump expression in the larynx of patients with LPR and laryngeal cancer was investigated herein. A human hypopharyngeal cell line expressing the proton pump was generated to investigate its effects. Study Design In‐vitro translational. Methods Laryngeal biopsies were obtained from three LPR and eight LSCC patients. ATP4A, ATP4B and HRPT1 were assayed via qPCR. Human hypopharyngeal FaDu cell lines stably expressing proton pump were created using lentiviral transduction and examined via transmission electron microscopy and qPCR for genes associated with inflammation or laryngeal cancer. Results Expression of ATP4A and ATP4B was detected in 3/3 LPR, 4/8 LSCC‐tumor and 3/8 LSCC‐adjacent specimens. Expression of ATP4A and ATP4B in FaDu elicited mitochondrial damage and expression of IL1B, PTGS2, and TNFA (P