Phenotypic changes of spleen macrophages in advanced gastric cancer and their effects on proliferation, invasion and migration of gastric cancer cells / 西安交通大学学报(医学版)

ABSTRACT

Objective: To investigate the phenotypic changes of splenic macrophages in advanced gastric cancer and the effects of co-culture with M1 and M2 macrophages on gastric cancer cells in order to explore the role of the spleen in the development of gastric cancer. Methods: We collected the fresh surgically removed spleens from 15 patients who had undergone advanced proximal gastrectomy combined with splenectomy in our hospital from March 2015 to May 2017. Spleen macrophages were isolated from these spleen tissues and the macrophage phenotypes were detected by flow cytometry. Monocytes were isolated from fresh blood of healthy volunteers using a fully automated bead extraction system; the identified monocytes were given 10 ng/mL of GM-CSF and M-CSF to be induced into M1-type macrophages and M2-type macrophages, respectively. The phenotypes of macrophages were identified by flow cytometry using CD16 and CD163; the gastric cancer cells SGC-7901 and AGS were co-cultured with M1, M2 macrophages and monocytes using Transwell co-culture method; trypan blue staining was used to detect the proliferative, invasive and migratory abilities of the cells. Results: The proportion of type M2 macrophages in the spleen of patients with advanced gastric cancer was increased while the proportion of type M1 macrophages decreased. The mononuclear cells were induced into M1 and M2 macrophages by culture with GM-CSFand M-CSF, and the positive rate of monocytes was (95.46±4.21)% and (94.67±4.97)%, respectively; M2 macrophages and monocytes could promote the invasion and migration of gastric cancer cells, while M1 macrophages inhibited the invasion and migration of gastric cancer cells. Conclusion: This study identified the proportions of different macrophages in spleen tissues of patients with advanced gastric cancer, and confirmed that the different types of macrophages on gastric cancer cells have different effects. M2 macrophages promoted gastric cancer cells, while M1 macrophages showed the effect of inhibiting gastric cancer cells. Our research further revealed the role of the spleen in the progression of gastric cancer and provided experimental research basis for formulating a treatment plan for advanced gastric cancer.