School of Clinical Medicine, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, PR China; Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, 42 Baiziting, Nanjing 210009, PR China; Department of General Surgery, the First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, PR China.
Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, 42 Baiziting, Nanjing 210009, PR China.
Exp Cell Res. 2018 Aug 1;369(1):129-138. doi: 10.1016/j.yexcr.2018.05.014. Epub 2018 May 17.
The subtypes of distant-organ metastasis led to treatment failure and poor prognosis are major obstacles in the management of patients with advanced breast cancer (BCa). Emerging evidences demonstrated that exosomes act as mediators for intercellular communication between various types of cells in the local tumor microenvironment. The present study aims to investigate whether BCa-derived exosomes are capable of cell-cell transferring miR-222 for BCa metastatic progression. Results showed that exosomal miR-222 is highly expressed in BCa patients with lymphatic metastasis. Consistently, the elevated levels of exosomal miR-222 are closely correlated with the high aggressivity of BCa cell lines. miR-222 promoting the aggressivity of BCa cells was confirmed in vitro and in vivo. Mechanistically, miR-222 directly targets PDLIM2, a tumor suppressor gene, leading to activation of NF-κB signal pathway. In conclusion, the levels of exosomal miR-222 are correlated with BCa metastatic progression. Exosome-transferred miR-222 promotes migration and invasion of BCa cells. miR-222 contributes to tumorigenicity of BCa cells through down-regulation of PDLIM2 and consequently activating NF-κB.
远处器官转移的亚型导致治疗失败和预后不良，是晚期乳腺癌（BCa）患者管理的主要障碍。新出现的证据表明，外泌体作为局部肿瘤微环境中各种类型细胞之间细胞间通讯的介质。本研究旨在探讨 BCa 来源的外泌体是否能够将 miR-222 细胞间转移用于 BCa 转移进展。结果表明，淋巴转移的 BCa 患者中外泌体 miR-222 表达水平较高。一致地，外泌体 miR-222 的升高水平与 BCa 细胞系的高侵袭性密切相关。miR-222 在体外和体内均证实可促进 BCa 细胞的侵袭性。在机制上，miR-222 直接靶向 PDLIM2，一种肿瘤抑制基因，导致 NF-κB 信号通路的激活。总之，外泌体 miR-222 的水平与 BCa 的转移进展相关。外泌体转移的 miR-222 促进 BCa 细胞的迁移和侵袭。miR-222 通过下调 PDLIM2 并继而激活 NF-κB 促进 BCa 细胞的致瘤性。
