Dectin3 protects against hepatocellular carcinoma by regulating glycolysis of macrophages.

BACKGROUND: Hepatocellular carcinoma (HCC) is among the commonest cancer and is high in incidence. Besides, glycolysis has been proven to be a promoter in cancer progression. But the research related to glycolysis concentrates on tumor cells, and few are about macrophages. Dectin3 is a C-type Lectin receptor (CLR), expressed by myeloid lineage cells such as monocytes/macrophages, which can recognize pathogens and modulate immunity. We speculate that Dectin3 is involved in HCC by regulating the glycolysis in macrophages, which is meaningful. METHODS: Wild-type (WT) mice and Dectin3-/- mice were used to establish a mouse model of HCC and the progression of HCC was evaluated. Primary tumor associated macrophages (TAMs) were isolated from tumor tissues and the level of glycolysis was assessed. WT and Dectin3-/- tumor-bearing mice were treated with glycolysis inhibitors and the tumor progression was assessed. Culture supernatant derived from H22 cells was used to stimulate bone-marrow-derived macrophages (BMDMs). The level of glycolysis in BMDMs was subsequently detected. H22 cells and BMDMs were co-cultured and then the proliferation and apoptosis of H22 cells were evaluated. RESULTS: Compared with WT mice, tumor volume of Dectin3-/- mice increased, and the proportion of macrophages in tumor tissues increased, while the proportions of CD4+ and CD8+T cells decreased. Besides, the splenomegaly of Dectin3-/- mice was more serious. The level of glycolysis in macrophages of Dectin3-/- tumor-bearing mice was significantly up-regulated. After glycolysis inhibitor treatment, cancer progression of Dectin3-/- tumor-bearing mice slowed down, and the difference between WT mice and Dectin3-/- mice was significantly down-regulated. In addition, Dectin3 deficiency macrophages significantly promoted H22 cell proliferation and inhibited H22 cell apoptosis. CONCLUSION: Dectin3 can protect against HCC. Dectin3 contributes to the apoptosis of tumor cells and inhibits the proliferation of tumor cells by regulating the glycolysis of macrophages.