Exosomes released from Doxorubicin-treated breast tumor promote lung metastasis through miR126 mediated induction of MDSCs (TUM10P.1060)

Abstract Chemotherapy induces myeloid-derived suppressor cells (MDSCs) which promote tumor metastasis. However, the molecular basis for chemotherapy induced MDSCs remains poorly understood. Here, we demonstrate that Doxorubicin-derived MDSC promote cancer progression via their effect on angiogenesis and the formation of a premetastatic niche. miRNA-containing exosomes from doxorubicin-treated MDSC exert more potent proangiogenic effects. We also demonstrate high level of MiR-126 was detected in Doxorubicin-derived exosomes, and inhibition of miR126 encapsulated in exosomes impaired proangiogenic effects of Doxorubicin-derived MDSC. Furthermore, nanoparticle-mediated targeting delivery of anti-miR-126 to MDSCs improves Doxorubicin-based therapeutic responses, leading to inhibition of lung metastasis. Collectively, our finding provides a compelling rationale to develop therapeutic strategy for overcoming chemotherapy resistance.