Overexpression of pigment epithelium-derived factor in breast cancer cell-derived exosomes induces M1 polarization in macrophages.

ABSTRACT

M2 macrophages, the major component of tumor microenvironment, are recognized as important player in tumor progression. M2 macrophages mediate this effect by promoting tumor angiogenesis, tumor metastasis, and suppression of tumor immunity. Reprogramming of M2 macrophages can serve as a promising strategy in cancer immunotherapy. In this study, we constructed pigment epithelium-derived factor (PEDF) expressing vector and transfected MDA-MB-231 cells with this construct. Then, exosomes were isolated from transfected cells and M2 macrophages were incubated with isolated exosomes from transfected cell. The effect of isolated exosomes on macrophage polarization was examined by real-time PCR and ELISA. The results demonstrated reprogramming of M2 macrophages after incubation with isolated exosomes from PEDF transfected cells. M2-to-M1 repolarization of macrophages was confirmed by upregulation of CD80, IRF5, MCP1, and IL-1ß and repression of CD206, Arg, TGM2, and TGF-ß. Therefore, these findings revealed that introducing PEDF into exosomes by genetic manipulation of parent cells may be a potential approach for reprogramming of M2 macrophages in cancer.