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Rectal cancer-derived exosomes activate the nuclear factor kappa B pathway and lung fibroblasts by delivering integrin beta-1

  • Qingkun Gao (Department of Gastrointestinal Surgery, Peking University Shougang Hospital) ;
  • Ke An (Department of Gastrointestinal Surgery, Peking University Shougang Hospital) ;
  • Zhaoya Gao (Department of Gastrointestinal Surgery, Peking University Shougang Hospital) ;
  • Yanzhao Wang (Department of Gastrointestinal Surgery, Peking University Shougang Hospital) ;
  • Changmin Ding (Department of Gastrointestinal Surgery, Peking University Shougang Hospital) ;
  • Pengfei Niu (Department of Gastrointestinal Surgery, Peking University Shougang Hospital) ;
  • Fuming Lei (Department of Gastrointestinal Surgery, Peking University Shougang Hospital)
  • Received : 2023.02.15
  • Accepted : 2023.04.21
  • Published : 2023.07.01

Abstract

Numerous studies have revealed the importance of tumor-derived exosomes in rectal cancer (RC). This study aims to explore the influence of tumor-derived exosomal integrin beta-1 (ITGB1) on lung fibroblasts in RC along with underlying mechanisms. Exosome morphology was observed using a transmission electron microscope. Protein levels of CD63, CD9, ITGB1, p-p65 and p65 were detected using Western blot. To determine ITGB1's mRNA expression, quantitative real-time polymerase chain reaction was used. Moreover, levels of interleukin (IL)-8, IL-1β, and IL-6 in cell culture supernatant were measured via commercial ELISA kits. ITGB1 expression was increased in exosomes from RC cells. The ratio of p-p65/p65 as well as levels of interleukins in lung fibroblasts was raised by exosomes derived from RC cells, while was reduced after down-regulation of exosomal ITGB1. The increased ratio of p-p65/p65 as well as levels of pro-inflammatory cytokines caused by exosomes from RC cells was reversed by the addition of nuclear factor kappa B (NF-κB) inhibitor. We concluded that the knockdown of RC cells-derived exosomal ITGB1 repressed activation of lung fibroblasts and the NF-κB pathway in vitro.

Keywords

Acknowledgement

This work was supported by Peking University Shougang Hospital Shouyi Medical Technology Development Fund (SGYYQ202010).

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