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

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.