IL-8/CXCR2 信号促进食管鳞癌细胞增殖，并与不良预后相关。

IL-8/CXCR2 Signalling Promotes Cell Proliferation in Oesophageal Squamous Cell Carcinoma and Correlates With Poor Prognosis.

机构信息

Department of Surgery, Keio University, School of Medicine, Tokyo, Japan.

Department of Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan

出版信息

Anticancer Res. 2021 Feb;41(2):783-794. doi: 10.21873/anticanres.14830.

DOI:10.21873/anticanres.14830

PMID:33517283

Abstract

BACKGROUND/AIM: The inflammatory cytokine IL-8 and its receptor CXCR2 are key signalling pathway molecules in cancer development. We hypothesized that IL-8/CXCR2 signalling promotes tumour progression in oesophageal squamous cell carcinoma (ESCC) patients.

MATERIALS AND METHODS

We examined the relationship between IL-8/CXCR2 expression and clinicopathological factors by immunohistochemistry in samples from 63 patients with resectable ESCC. The effects of IL-8/CXCR2 signalling on cell proliferation and gene expression were examined in vitro and in vivo using ESCC cell lines.

RESULTS

Increased IL-8/CXCR2 signalling was associated with shorter overall survival (p<0.05) and recurrence-free survival (p<0.05) in ESCC patients. Multivariate analysis identified IL-8/CXCR2 expression as a prognostic factor for surgically treated ESCC (p<0.05). In vitro, IL-8 exposure or over-expression significantly enhanced ESCC cell proliferation. SB225002, a CXCR2-specific antagonist, and IL-8 siRNA significantly suppressed cell proliferation.

CONCLUSION

IL-8/CXCR2 expression is an independent prognostic factor for surgically treated ESCC, and IL-8/CXCR2 signalling contributes to ESCC cell proliferation.

摘要

背景/目的：炎症细胞因子 IL-8 和其受体 CXCR2 是癌症发展中关键的信号通路分子。我们假设 IL-8/CXCR2 信号促进食管鳞状细胞癌（ESCC）患者的肿瘤进展。

材料和方法

我们通过免疫组织化学方法检查了 63 例可切除 ESCC 患者样本中 IL-8/CXCR2 表达与临床病理因素之间的关系。我们使用 ESCC 细胞系在体外和体内研究了 IL-8/CXCR2 信号对细胞增殖和基因表达的影响。

结果

IL-8/CXCR2 信号的增加与 ESCC 患者的总生存（p<0.05）和无复发生存（p<0.05）较短有关。多变量分析确定 IL-8/CXCR2 表达是手术治疗 ESCC 的预后因素（p<0.05）。在体外，IL-8 暴露或过表达显著增强了 ESCC 细胞的增殖。CXCR2 特异性拮抗剂 SB225002 和 IL-8 siRNA 显著抑制了细胞增殖。