title: As an independent unfavorable prognostic factor, IL-8 promotes metastasis of nasopharyngeal carcinoma through induction of epithelial-mesenchymal transition and activation of AKT signaling.
abstract: Nasopharyngeal carcinoma (NPC) has the highest metastatic potential among head and neck cancers. Distant metastasis is the major cause of treatment failure. The role of interleukin-8 (IL-8) in NPC progression remains unknown. Our multivariate survival analyses of 255 patients with NPC revealed that higher IL-8 expression in primary NPC tissue was an independent prognostic factor for overall survival, disease-free survival, and distant metastasis-free survival of the patients. In vitro study revealed that IL-8 was highly expressed in the established high-metastasis NPC clone S18 relative to the low-metastasis cells. Suppression of IL-8 by short-hairpin RNA reduced the expression of IL-8 in S18 cells and subsequently inhibited migration, invasion, and hepatic metastasis of the cells without influencing cellular growth. Overexpression of IL-8 in S26 cells resulted in increased migration, invasion, and metastasis capabilities of the cells without affecting cellular growth. Exogenous IL-8 enhanced the migration and invasion of low-metastasis CNE-2 cells in a dose-dependent manner. An epithelial-mesenchymal transition (EMT) could be induced by IL-8 in various NPC cell lines. The high level of phosphorylated AKT in S18 cells could be suppressed by knocking down IL-8 expression. Further, IL-8-promoted migration and invasion could be abolished by either the application of the phosphoinositide-3-kinase inhibitor LY294002 or the knock down of AKT expression by using small-interfering RNA. In summary, IL-8 serves as an independent prognostic indicator of overall survival, disease-free survival, and metastasis-free survival for patients with NPC. IL-8 promotes NPC metastasis via autocrine and paracrine means, involving activation of AKT signaling and inducing EMT in NPC cells.
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, Guangdong 510060, P R China.
authors.forename: Xin-Jian
authors.initials: XJ
authors.lastname: Li
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Peng
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Shao
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Lu
authors.forename: Jia-Xing
authors.initials: JX
authors.lastname: Zhang
authors.forename: Shi
authors.initials: S
authors.lastname: Chen
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Chen
authors.forename: Yan-Qun
authors.initials: YQ
authors.lastname: Xiang
authors.forename: Ying-Na
authors.initials: YN
authors.lastname: Bao
authors.forename: Fang-Jing
authors.initials: FJ
authors.lastname: Zheng
authors.forename: Mu-Sheng
authors.initials: MS
authors.lastname: Zeng
authors.forename: Tie-Bang
authors.initials: TB
authors.lastname: Kang
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.forename: Bin Tean
authors.initials: BT
authors.lastname: Teh
authors.forename: Chao-Nan
authors.initials: CN
authors.lastname: Qian
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D016209:Interleukin-8 / Q000502:physiology*; D009303:Nasopharyngeal Neoplasms / Q000201:enzymology / Q000473:pathology*; D009362:Neoplasm Metastasis; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D017931:DNA Primers; D016209:Interleukin-8; D051057:Proto-Oncogene Proteins c-akt