Microrna-100/Mtor/Il-1ra Signaling Maintains Tams Phenotype And Enhances Tumor Cell Sternness Property In Mouse Breast Cancer

Tumor-associated macrophages(TAMs),the main part of immune cells in tumor microenvironment(TME),play a potent role in promoting tumorigenesis. MicroRNAs (miRs) are considered to be crucial regulators in tumor progression. However, the role that miRs play in TAMs phenotype regulation still remains unclear. In this study, we demonstrated that miR-100 played an important role in maintaining TAMs phenotype and enhancing tumor stemness properties. First, miRNome of TAMs isolated from mouse breast tumor was performed. Compared with macrophages from normal spleen, 40 miRs candidates, in 150 TAMs-high and 169 TAMs-low expressed miRs which were selected from miRNome, were further identified by real-time PCR. Importantly, miR-100 was found with TAMs-high expression pattern(about 70 folds changes). Moreover, we found that miR-100 overexpressed RAW264.7 cells and peritoneal macrophages gained M2 phenotype such as CD206+ cells percentage. Mechanism study demonstrated that miR-100 up-regulated IL-1ra expression detected by cytokine array. Furthermore we found that IL-1ra could enhance 4T1 breast cancer cell stemness properties including increasing tumor cell sphere formation and drug resistance in vitro. Taken together, our results demonstrate that TAMs-high expressed miR-100 could function to maintain the phenotype of TAMs via targeting mTOR pathway, and promote tumorigenesis by enhancing IL-1ra secretion, which would also serve as a promising therapy target to remodel TME and tumor metastasis. Citation Format: Wei Wang, Yan Liu, Jian Guo, Huiwen He, Junling Xie, Chong Chen, Yunping Luo. MicroRNA-100/mTOR/IL-1ra signaling maintains TAMs phenotype and enhances tumor cell stemness property in mouse breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 724.