M1 macrophage-derived exosomal microRNA-29c-3p suppresses aggressiveness of melanoma cells via ENPP2

In the tumor microenvironment, macrophages play crucial roles resulting in tumor suppression and progression, depending on M1 and M2 macrophages, respectively. In particular, macrophage-derived exosomes modulate the gene expression of cancer cells by delivering miRNAs which downregulate specific genes. The communication between macrophages and cancer cells is especially important in immunogenic tumors such as melanoma, where the cancer pogression is significantly influenced by the surrounding immune cells. In this study, we identified that M1 macrophages secrete exosomal miR-29c-3p in the co-culture system with melanoma cells. Simultaneously, ENPP2, the target of miR-29c-3p, decreased in the melanoma cells which are co-cultured with M1 macrophages. Additionally, we observed that the reduction of ENPP2 alleviates melanoma cell migration and invasion, due to the changes of cholesterol metabolism and ECM remodeling. Based on these findings, we demonstrated that M1 macrophages suppress aggressiveness of melanoma cells via exosomal miR-29c-3p-mediated knock-down of ENPP2 in cancer cells. Graphical Abstract: (Figure presented.)