IL-8 promotes HNSCC progression on CXCR1/2-meidated NOD1/RIP2 signaling pathway

Leong-Perng Chan,Ling-Feng Wang,Feng-Yu Chiang,Po-Lin Kuo,Chia-Hua Liang,Ka-Wo Lee

doi:10.18632/oncotarget.11445

Abstract

NOD1 (nucleotide-binding oligomerization domain 1) is overexpressed in head and neck squamous cell carcinoma (HNSCC) cells, as is IL-8 in cancer cells. However, the mechanism of the IL-8-mediated overexpression of NOD in HNSCC not been identified. This study determines whether IL-8 promotes tumor progression via the NOD signaling pathway in HNSCC. Higher IL-8, NOD1 and receptor-interacting protein kinase (RIP2) expressions were observed in HNSCC tissue than in non-cancerous matched tissue (NCMT), whereas NOD2 was weakly expressed. Furthermore, IL-8 stimulated the proliferation of HNSCC cells (SCC4, SCC9 and SCC25) but not dysplastic oral mucosa DOK cells. Exposure to IL-8 increased the clonogenicity of HNSCC cells. IL-8 siRNA inhibited cell proliferation and cell colony formation, suggesting that IL-8 is involved in HNSCC cancer progression. The expressions of CXCR1 and CXCR2 were higher in HNSCC tissue than in NCMT. HNSCC cells that were exposed to IL-8 exhibited higher expression of CXCR1/2 than did controls. The blocking of IL-8 by siRNA reduced CXCR1/2 expression in HNSCC cells, suggesting that the cancer progression of HNSCC cells that is induced by IL-8 depends on CXCR1/2. Additionally, IL-8 is associated with increased NOD1 and RIP2 expression and reduced NOD2 expression in three types of HNSCC cells. The blocking of IL-8 by siRNA reduces IL-8, NOD1 and RIP2 expressions in HNSCC cells, but not the level of NOD2. These results suggest that IL-8 has an important role in HNSCC progression via a CXCR1/2-meidated NOD1/RIP2 signaling pathway.

Highlights

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world
The results revealed that the knockdown of IL-8 reduced nucleotide binding oligomerization domain (NOD)-mediated RIP2 activation in three types of HNSCC cell, while IL-8 siRNA treatment did not affect the expression of NOD2, according to RT-PCR (Figure 6C) and western blotting (Figure 6D)
Previous reports have demonstrated that salivary IL-8 levels in oral lichen planus (OLP) patients are significantly reduced by treatment with dexamethasone, revealing that levels of IL-8 are affected by inflammation in OLP

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world. Predominantly oral SCC (OSCC), is a high-impact disease of the oral cavity. OSCC is generally detected in the late stages when the cancer has advanced, and has a poor prognosis and survival rate [1]. Surgery and radiotherapy are currently the primary treatments, but they typically cause postoperative defects and functional impairments in patients owing to the location of OSCC in the head and neck [2]. Since morbidity and mortality rates associated with HNSCC have improved very little over the past 30 years, early detection or prevention of the disease is likely to be most effective. Basic research into HNSCC is increasing, focusing on the identification of specific biomarkers for the diagnosis of its nature and aggressiveness [3]

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Conclusion