Abstract 2828: miR-19a-3p inhibits breast carcinoma metastasis via reversing M2 phenotype of TAMs.

Tumor-associated macrophages (TAMs), most of which exhibit M2 phenotype, function as immunosuppressive cells in tumor microenvironment (TME). Polarization of TAMs from a pro-immune (M1 like) phenotype to an immune-suppressive (M2-like) phenotype is one of the hallmarks of malignancy, but their molecular basis is still remains unknown. It has been reported that microRNAs are involved in monocyte-macrophage differentiation. In this study, we found that miR-19a-3p, broadly conserved in vertebrate, could reverse the M2 phenotype of RAW macrophage cells. When mouse breast tumor cells such as 4T1, 4TO7 and EMT6 were co-cultured with RAW macrophage cells which over express miR-19a-3p, the invasion capacity was suppressed. Meanwhile, when the conditional medium of RAW cells which were transfected with miR-19a-3p mimic was added into culturing medium of tumor cells, the migration capacity of 4T1 and EMT6 breast cancer cells was inhibited. Moreover, when miR-19a-3p was injected intratumor, consistent with the in vitro experiments, we found that the M2 phenotype of TAMs was suppressed significantly. Although 4T1 xengraft breast tumor growth was not affected by miR-19a-3p, lung metastasis of tumor cells was significantly suppressed. Taken together, our findings indicate that miR-19a-3p is down-regulated in M2 phenotype RAW macrophage and TAMs in TME. The low expression of miR-19a-3p plays an important role in inducing M2 macrophage polarization and promoting migration and invasion capacity and metastasis. Citation Format: Jian Yang, Na Li, Zhuhong Zhang, Qin Si, Chong Chen, Yan Liu, Ralph A. Reisfeld, Peiqing Sun, Dwayne Stupack, Rong Xiang, Yunping Luo. miR-19a-3p inhibits breast carcinoma metastasis via reversing M2 phenotype of TAMs. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2828. doi:10.1158/1538-7445.AM2013-2828 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.