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

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-vitrotranslational. Methods Laryngeal biopsies were obtained from three LPR and eight LSCC patients.ATP4A,ATP4BandHRPT1were 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 ofATP4AandATP4Bwas detected in 3/3 LPR, 4/8 LSCC-tumor and 3/8 LSCC-adjacent specimens. Expression ofATP4AandATP4Bin FaDu elicited mitochondrial damage and expression ofIL1B,PTGS2, andTNFA(P< .0001); expression ofATP4Balone did not. Conclusions Gastric proton pump subunits are expressed in the larynx of LPR and LSCC patients. Mitochondrial damage and changes in gene expression observed in cells expressing the full proton pump, absent in those expressing a single subunit, suggest that acid secretion by functional proton pumps expressed in upper airway mucosa may elicit local cell and molecular changes associated with inflammation and cancer. Level of Evidence NALaryngoscope, 2020

Automated summary

The study found expression of gastric proton pump subunits in the larynx of patients with laryngopharyngeal reflux (LPR) and laryngeal squamous cell carcinoma (LSCC). Cells expressing the full proton pump exhibited mitochondrial damage and changes in gene expression associated with inflammation and cancer, indicating that functional proton pump expression in upper airway mucosa may lead to local cellular and molecular changes with pathological implications.