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

癌症相关巨噬细胞分泌的 IL-10 通过 c-Met/STAT3 信号传导调节胃癌细胞的增殖和侵袭

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作者:Ling Chen, Yuntao Shi, Xiaojuan Zhu, Weiwei Guo, Mingjiong Zhang, Ying Che, Lijuan Tang, Xiaozhong Yang, Qiang You, Zheng Liu

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.

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