Pepsin promotes laryngopharyngeal neoplasia by modulating signaling pathways to induce cell proliferation

Kai Niu; Chunjie Guo; Shiyong Teng; Dandan Zhou; Shuyuan Yu; Wanzhong Yin; Ping Wang; Wei Zhu; Maoli Duan

doi:10.1371/journal.pone.0227408

Pepsin promotes laryngopharyngeal neoplasia by modulating signaling pathways to induce cell proliferation

PLoS One. 2020 Jan 15;15(1):e0227408. doi: 10.1371/journal.pone.0227408. eCollection 2020.

Authors

Kai Niu¹, Chunjie Guo², Shiyong Teng³, Dandan Zhou², Shuyuan Yu¹, Wanzhong Yin¹, Ping Wang¹, Wei Zhu¹, Maoli Duan⁴

Affiliations

¹ Department of Otolaryngology Head and Neck Surgery, the First Hospital of Jilin University, Changchun, PR China.
² Department of Radiology, the First Hospital of Jilin University, Changchun, PR China.
³ Department of Anesthesiology, the First Hospital of Jilin University, Changchun, PR China.
⁴ Department of Clinical Science, Intervention and Technology, Department of Otolaryngology Head and Neck Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.

Abstract

Pepsin plays an important role in laryngopharyngeal reflux (LPR), a risk factor for the development of hypopharyngeal squamous cell carcinomas (HPSCC). However, the role of pepsin in HPSCC is not clear. We show by immunohistochemistry that pepsin positivity occurs in a significant proportion of human primary HPSCC specimens, and in many cases matched adjacent uninvolved epithelia are negative for pepsin. Pepsin positivity is associated with nodal involvement, suggesting that pepsin may have a role in metastasis. Treatment of FaDu cancer cells with pepsin increased cell proliferation, possibly by inducing G1/S transition. We also observed significant changes in expression of genes involved in NF-kappaB, TRAIL and Notch signaling. Our data suggest that pepsin plays an important role in HPSCC and that targeting pepsin could have potential therapeutic benefits.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Carcinoma, Squamous Cell / metabolism*
Carcinoma, Squamous Cell / pathology
Cell Line, Tumor
Female
G1 Phase*
Gene Expression Regulation, Neoplastic*
Humans
Laryngeal Neoplasms / metabolism*
Laryngeal Neoplasms / pathology
Male
Middle Aged
Neoplasm Metastasis
Neoplasm Proteins / metabolism*
Pepsin A / metabolism*
Pepsin A / pharmacology
Pharyngeal Neoplasms / metabolism*
Pharyngeal Neoplasms / pathology
S Phase*
Signal Transduction*

Substances

Neoplasm Proteins
Pepsin A

Grants and funding

This work received a grant from Jilin Provincial Department of Health, China (Grant number 20132016) to KN and WY. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.