Neutrophils Promote Larynx Squamous Cell Carcinoma Progression via Activating the IL-17/JAK/STAT3 Pathway.

Tianyi Liu,Yang Jiang,Qingquan Hua,Jie Wang,Rui Zhao,Shimin Zong,Xiao-Jie Lu

doi:10.1155/2021/8078646

Abstract

Laryngeal squamous cell carcinoma (LSCC) is the main type of laryngeal cancer with poor prognosis. Incidence of LSCC increases every year, posing a great threat to human health. The underlying mechanism needs further study. Neutrophils are the most prevalent type of immune cells, which play vital roles in crosstalk between the microenvironment and cancer cells. In our study, we aim to figure out the complex regulation between neutrophils and LSCC. Our experiments showed that LSCC cells could promote the activation and mobility of neutrophils. And, in return, neutrophils enhanced the proliferation, migration, and invasion of LSCC. The subsequent results showed that IL-17 was highly expressed in neutrophil conditioned medium. Block of IL-17 could effectively inhibit the progression of LSCC induced by neutrophils. What is more, the results showed that IL-17 activated the JAK/STAT3 pathway in LSCC. Inhibition of the JAK/STAT3 pathway could significantly block neutrophil-induced LSCC progression. Our research reveals the complex interaction between neutrophils and LSCC cells, providing new ideas for the treatment of LSCC.

Highlights

Laryngeal squamous cell carcinoma (LSCC) is generated from the laryngeal mucosal epithelium
The neutrophils were cocultured with RPMI-1640 medium with 10% FBS, RPMI-1640 with 1.25% dimethyl sulfoxide (DMSO) and 10% FBS, conditioned medium of Tu177 and Tu686, and conditioned medium of Tu177 and Tu686 with 1.25% DMSO, respectively. qRT-PCR analysis revealed that the conditioned medium of Tu177 and Tu686 could significantly upregulate CD11b, CD18, and MPO levels compared with the control group (Figures 1(a)–1(g))
Our results showed that neutrophils activated the JAK/STAT3 pathway, and blockage of IL-17 could effectively reduce the activation of the JAK/STAT3 pathway (Figures 4(a) and 4(b))

Summary

Introduction

Laryngeal squamous cell carcinoma (LSCC) is generated from the laryngeal mucosal epithelium. LSCC accounts for 2.4% of systemic malignancies and more than 90% of laryngeal carcinoma [1]. More than 90,000 people died of LSCC every year. LSCC patients suffer from severe impairments in breathing and swallowing, which cause great pain. More than half of the patients are diagnosed in an advanced stage [2]. LSCC patients’ survival is seriously affected by local invasion and metastasis [3]. It is of great importance to figure out the mechanism of LSCC progression and find new targets for therapy

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Conclusion