Research Papers:

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

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

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Oncotarget. 2016; 7:61820-61831. https://doi.org/10.18632/oncotarget.11445

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Leong-Perng Chan1,2, Ling-Feng Wang2, Feng-Yu Chiang2, Ka-Wo Lee2, Po-Lin Kuo1,3, Chia-Hua Liang4

1Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

2Department of Otolaryngology-Head and Neck Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

3Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung, Taiwan

4Department of Cosmetic Science and Institute of Cosmetic Science, Chia Nan University of Pharmacy and Science, Tainan, Taiwan

Correspondence to:

Po-Lin Kuo, email: [email protected]

Chia-Hua Liang, email: [email protected]

Keywords: HNSCC, IL-8, NOD1, cancer progression

Received: May 15, 2016     Accepted: August 13, 2016     Published: August 20, 2016


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.

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