Exosomes derived from hypoxic epithelial ovarian cancer deliver microRNA-940 to induce macrophage M2 polarization

Hypoxia is a common feature of solid tumors. It is closely related to tumor progression. Exosomal microRNAs derived from cancers are considered to be mediators between cancer cells and the tumor microenvironment. In addition, the number of tumor-associated macrophages (TAMs) in the tumor microenvironment has also been demonstrated to correlate with tumor development. However, the relationship between tumor-secreted exosomes and TAM polarization under hypoxic conditions during tumor progression is not clear. Herein, we demonstrated that hypoxia induces the high expression of microRNA-940 (miR-940) in exosomes derived from epithelial ovarian cancer (EOC). We also found that miR-940 is highly expressed in exosomes isolated from ascites of EOC patients. Moreover, the overexpression of miR-940 in macrophages delivered by exosomes stimulated M2 phenotype polarization, while the M2 subtype macrophages promoted EOC proliferation and migration. These results highlight the function of hypoxia in enhancing the high level of expression of miR-940 in tumor exosomes taken up by macrophages. We also showed that the tumor-promoting function of miR-940 is mediated by TAM polarization in EOC. These findings show that tumor-derived exosomal miR-940 induced by hypoxia plays an important role in stimulating TAM polarization in the progression of EOC.