IL-8/CXCR2 signalling promotes cell proliferation in oesophageal squamous cell carcinoma and correlates with poor prognosis

Masazumi Inoue, Hiroya Takeuchi, Sachiko Matsuda, Tomohiko Nishi, Kazumasa Fukuda, Rieko Nakamura, Tsunehiro Takahashi, Norihito Wada, Hirofumi Kawakubo, Yuko Kitagawa

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)783-794
Number of pages12
JournalAnticancer research
Volume41
Issue number2
DOIs
Publication statusPublished - 2021 Feb

Keywords

  • CXCR2
  • Cell proliferation
  • Chemokine
  • IL-8
  • Oesophageal squamous cell carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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