Pepsin promotes IL-8 signaling-induced epithelial–mesenchymal transition in laryngeal carcinoma
Abstract Background Laryngopharyngeal reflux (LPR), with its increasing morbidity, is attracting considerable attention. In recent years, the causal role between LPR and laryngeal carcinoma has been debated. The main harmful component of LPR is pepsin, which has been shown to induce mucosal inflamma...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2019-03-01
|
Series: | Cancer Cell International |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s12935-019-0772-7 |
id |
doaj-0e7eb28b1d6b4cb399a8e2de2180e757 |
---|---|
record_format |
Article |
spelling |
doaj-0e7eb28b1d6b4cb399a8e2de2180e7572020-11-25T01:39:23ZengBMCCancer Cell International1475-28672019-03-0119111310.1186/s12935-019-0772-7Pepsin promotes IL-8 signaling-induced epithelial–mesenchymal transition in laryngeal carcinomaJia-Jie Tan0Lu Wang1Ting-Ting Mo2Jie Wang3Mei-Gui Wang4Xiang-Ping Li5Department of Otolaryngology, Head and Neck Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Otolaryngology, Head and Neck Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Otolaryngology, Head and Neck Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Otolaryngology, Head and Neck Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Otolaryngology, Head and Neck Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Otolaryngology, Head and Neck Surgery, Nanfang Hospital, Southern Medical UniversityAbstract Background Laryngopharyngeal reflux (LPR), with its increasing morbidity, is attracting considerable attention. In recent years, the causal role between LPR and laryngeal carcinoma has been debated. The main harmful component of LPR is pepsin, which has been shown to induce mucosal inflammation by damaging the mucous membrane. Thus, pepsin is linked to an increased risk of laryngeal carcinoma, although the potential mechanism remains largely unknown. Methods The human laryngeal carcinoma cell lines Hep-2 and Tu212 were exposed to different pepsin concentrations and the morphology, proliferation, migration, secretion of inflammatory cytokines, and epithelial–mesenchymal transition (EMT) of the cells were assessed. To evaluate whether interleukin-8 (IL-8) had a causal relationship with pepsin and EMT, an IL-8 inhibitor was used to suppress IL-8 secretion during pepsin exposure and the expression of EMT markers, cell proliferation, and migration were analyzed. Results Pepsin promoted proliferation, colony formation, migration, and IL-8 secretion of Hep-2 and Tu212 cells in vitro. Furthermore, increased pepsin concentrations changed the morphology of Hep-2 and Tu212 cells; levels of the epithelial marker E-cadherin were reduced and those of mesenchymal markers vimentin and β-catenin and the transcription factors snail and slug were elevated. A similar effect was observed in laryngeal carcinoma tissues using immunohistochemistry. IL-8 level was reduced and EMT was restored when pepsin was inhibited by pepstatin. EMT was weakened after exposure to the IL-8 inhibitor, with significant reduction in pepsin-induced cell proliferation and migration. Conclusions Pepsin may induce EMT in laryngeal carcinoma through the IL-8 signaling pathway, which indicates that it has potential role in enhancing cell proliferation and metastasis of laryngeal carcinoma.http://link.springer.com/article/10.1186/s12935-019-0772-7Laryngopharyngeal refluxLaryngeal carcinomaPepsin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jia-Jie Tan Lu Wang Ting-Ting Mo Jie Wang Mei-Gui Wang Xiang-Ping Li |
spellingShingle |
Jia-Jie Tan Lu Wang Ting-Ting Mo Jie Wang Mei-Gui Wang Xiang-Ping Li Pepsin promotes IL-8 signaling-induced epithelial–mesenchymal transition in laryngeal carcinoma Cancer Cell International Laryngopharyngeal reflux Laryngeal carcinoma Pepsin |
author_facet |
Jia-Jie Tan Lu Wang Ting-Ting Mo Jie Wang Mei-Gui Wang Xiang-Ping Li |
author_sort |
Jia-Jie Tan |
title |
Pepsin promotes IL-8 signaling-induced epithelial–mesenchymal transition in laryngeal carcinoma |
title_short |
Pepsin promotes IL-8 signaling-induced epithelial–mesenchymal transition in laryngeal carcinoma |
title_full |
Pepsin promotes IL-8 signaling-induced epithelial–mesenchymal transition in laryngeal carcinoma |
title_fullStr |
Pepsin promotes IL-8 signaling-induced epithelial–mesenchymal transition in laryngeal carcinoma |
title_full_unstemmed |
Pepsin promotes IL-8 signaling-induced epithelial–mesenchymal transition in laryngeal carcinoma |
title_sort |
pepsin promotes il-8 signaling-induced epithelial–mesenchymal transition in laryngeal carcinoma |
publisher |
BMC |
series |
Cancer Cell International |
issn |
1475-2867 |
publishDate |
2019-03-01 |
description |
Abstract Background Laryngopharyngeal reflux (LPR), with its increasing morbidity, is attracting considerable attention. In recent years, the causal role between LPR and laryngeal carcinoma has been debated. The main harmful component of LPR is pepsin, which has been shown to induce mucosal inflammation by damaging the mucous membrane. Thus, pepsin is linked to an increased risk of laryngeal carcinoma, although the potential mechanism remains largely unknown. Methods The human laryngeal carcinoma cell lines Hep-2 and Tu212 were exposed to different pepsin concentrations and the morphology, proliferation, migration, secretion of inflammatory cytokines, and epithelial–mesenchymal transition (EMT) of the cells were assessed. To evaluate whether interleukin-8 (IL-8) had a causal relationship with pepsin and EMT, an IL-8 inhibitor was used to suppress IL-8 secretion during pepsin exposure and the expression of EMT markers, cell proliferation, and migration were analyzed. Results Pepsin promoted proliferation, colony formation, migration, and IL-8 secretion of Hep-2 and Tu212 cells in vitro. Furthermore, increased pepsin concentrations changed the morphology of Hep-2 and Tu212 cells; levels of the epithelial marker E-cadherin were reduced and those of mesenchymal markers vimentin and β-catenin and the transcription factors snail and slug were elevated. A similar effect was observed in laryngeal carcinoma tissues using immunohistochemistry. IL-8 level was reduced and EMT was restored when pepsin was inhibited by pepstatin. EMT was weakened after exposure to the IL-8 inhibitor, with significant reduction in pepsin-induced cell proliferation and migration. Conclusions Pepsin may induce EMT in laryngeal carcinoma through the IL-8 signaling pathway, which indicates that it has potential role in enhancing cell proliferation and metastasis of laryngeal carcinoma. |
topic |
Laryngopharyngeal reflux Laryngeal carcinoma Pepsin |
url |
http://link.springer.com/article/10.1186/s12935-019-0772-7 |
work_keys_str_mv |
AT jiajietan pepsinpromotesil8signalinginducedepithelialmesenchymaltransitioninlaryngealcarcinoma AT luwang pepsinpromotesil8signalinginducedepithelialmesenchymaltransitioninlaryngealcarcinoma AT tingtingmo pepsinpromotesil8signalinginducedepithelialmesenchymaltransitioninlaryngealcarcinoma AT jiewang pepsinpromotesil8signalinginducedepithelialmesenchymaltransitioninlaryngealcarcinoma AT meiguiwang pepsinpromotesil8signalinginducedepithelialmesenchymaltransitioninlaryngealcarcinoma AT xiangpingli pepsinpromotesil8signalinginducedepithelialmesenchymaltransitioninlaryngealcarcinoma |
_version_ |
1725049275251949568 |