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.

Prognostic and Predictive Value of Cadherin 11 for Patients with Gastric Cancer and Its Correlation with Tumor Microenvironment: Results from Microarray Analysis

“…As inducers, CCL2, TGFB1, CXCL12, and MMP2 not only recruit more macrophages into the TME but also facilitate their polarization and the generation of more M2 macrophages [ 12 , 54 – 58 ]. High expression of M2-related markers often reflects the increased proportion of M2 macrophages in the TME [ 20 , 37 , 59 ]. These findings reflect the potential capability of CDH11 to induce macrophages into the TME and accelerate the transformation of M1 to M2 by interacting with cytokines and finally regulate the formation of the immune microenvironment.…”

“…In GC patients, a high level of M2 macrophages is associated obviously with the status of peritoneal dissemination, angiogenesis, immune evasion, and poor prognosis [16][17][18][19]. Ectopic expression of genes in tumor tissues can induce immune cells into the tumor microenvironment (TME), directly or indirectly, with the help of inflammatory mediators secreted by GC cells or infiltrating cells [20][21][22][23].…”

Macrophage and Tumor Cell Cross-Talk Is Fundamental for Lung Tumor Progression: We Need to Talk

“…TAMsderived IL10 perform several tasks in lung cancer progression and development (123). Similar to IL6, crosstalk within different cells of the TME via TAMs-derived IL10 leads to the activation of STAT3 (124,125). Additionally, TAM-derived IL10 promotes the stemness of lung cancer via JAK1/STAT1/NFKB/NOTCH1 signaling pathways in vivo tumorigenesis mouse models (126).…”

Immunological Aspects of the Tumor Microenvironment and Epithelial-Mesenchymal Transition in Gastric Carcinogenesis

“…The levels of IL-10 are significantly increased in both the tumor tissue and serum of GC patients. IL-10 has been found to influence GC invasiveness and migratory ability in vitro through the activation of the c-MET/JAK3 pathway [165]. Finally, there is a positive correlation between high expression of CCL5 and CD68 in GC cells.…”