Epithelial ovarian cancer-secreted exosomal miR-222-3p induces polarization of tumor-associated macrophages

// Xiang Ying 1, * , Quanfeng Wu 1, * , Xiaoli Wu 1 , Qinyi Zhu 1 , Xinjing Wang 1 , Lu Jiang 1 , Xin Chen 1 , Xipeng Wang 1 1 Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China * These authors are contributed equally to this work Correspondence to: Xipeng Wang, email: xipengwang@hotmail.com Keywords: exosomes, miR-222-3p, macrophage, polarization, epithelial ovarian cancer Received: February 18, 2016      Accepted: April 19, 2016      Published: May 09, 2016 ABSTRACT Cancer secreted exosomal miRNAs are emerging as mediators between tumor-stoma crosstalk. Here, we show epithelial ovarian cancer (EOC)-derived exosomes activated macrophages to a tumor-associated macrophage (TAM)-like phenotype with SOCS3/STAT3 pathway involvement, which could facilitate the progression of cancer. MiR-222-3p was enrichment in exosomes released from EOC cells and it could be transferred to macrophages. Overexpression of miR-222-3p in macrophages induced polarization of the M2 phenotype. Luciferase assay verified miR-222-3p targeted SOCS3 genes and expression of SOCS3 was decreased after transfection with a miR-222-3p mimic. Down-regulation of SOCS3 correlated with an increased expression of STAT3 activation. MiR-222-3p could be detected in the exosomes from serum and its levels were related to EOC. These observations propose tumor-derived exosomal miR-222-3p is an effective regulator in the polarization of tumor-promoting M2 macrophages and may be a biomarker of EOC.