IL‑10 secreted by cancer‑associated macrophages regulates proliferation and invasion in gastric cancer cells via c‑Met/STAT3 signaling

Oncol Rep. 2019 Aug;42(2):595-604. doi: 10.3892/or.2019.7206. Epub 2019 Jun 19.

Abstract

Gastric cancer is one of the most common types of human cancer, and it is additionally one of the leading causes of cancer‑associated mortality worldwide. Previous studies have suggested that interleukin (IL)‑10 may contribute to the pathogenesis of gastric cancer. However, the underlying mechanisms remain unclear. In the present study, it was observed that the expression of IL‑10 was significantly upregulated in gastric tumor tissues and serum samples of patients with gastric cancer. Furthermore, IL‑10 was increased in the cell culture supernatant of cancer‑associated macrophages (CAMs). Treatment with cell culture supernatant from CAMs induced a significant increase in proliferation and migration, while it suppressed apoptosis, in MGC‑803 and BGC‑823 gastric cancer cells. Notably, application of an inhibitory IL‑10 antibody partially blocked the cell culture supernatant of CAM‑induced oncogenic effects. RNA‑sequencing analysis was then performed to identify the differentially expressed genes in MGC‑803 cells treated with IL‑10. Based on the sequencing results and in vitro analysis, it was demonstrated that IL‑10‑induced carcinogenic behaviors in MGC‑803 cells were potentially mediated by activation of the c‑Met/STAT3 signaling pathway. In conclusion, the present results demonstrated that IL‑10 secreted by CAMs may be involved in the pathogenesis of gastric cancer, suggesting that IL‑10 may serve as a potential therapeutic target for the treatment of gastric cancer.

MeSH terms

  • Aged
  • Apoptosis
  • Biomarkers, Tumor / metabolism*
  • Case-Control Studies
  • Cell Proliferation*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interleukin-10 / metabolism*
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins c-met / metabolism*
  • STAT3 Transcription Factor / metabolism*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • IL10 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Interleukin-10
  • MET protein, human
  • Proto-Oncogene Proteins c-met