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TWEAK-stimulated macrophages inhibit metastasis of epithelial ovarian cancer via exosomal shuttling of microRNA

机译：调整刺激的巨噬细胞通过微润荷的外泌体血管抑制上皮细胞癌的转移

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摘要

Exosomal-miRNAs are emerging as mediators of crosstalk between tumor cells and macrophages. In this study, we observed that exosomes derived from TWEAK-stimulated macrophages (TMs) could be internalized by epithelial ovarian cancer (EOC) cells and inhibit cell metastasis. Through a miRNA microarray analysis, we identified 19 miRNAs that are differentially expressed in exosomes derived from macrophages treated with or without TWEAK. The study validated that TWEAK not only increased the levels of microRNA-7 (miR-7) in macrophages and its secreted exosomes but also resulted in an elevated level of miR-7 in recipient EOC cells, which eventually reduced the activity of the EGFR/AKT/ERK1/2 pathway. Pre-transfection of antagomiR-7 in TMs substantially decreased the levels of miR-7 in macrophages, its secreted exosomes and the recipient EOC cells with a concomitant enhancement of EOC metastasis, suggesting an involvement of exosomal miR-7 from TMs in modulating the metastasis of EOC cells. Finally, the exosomes from TMs significantly blocked EOC metastasis in a xenograft mouse model. These findings provide a novel model in which TMs inhibit the metastasis of EOC cells via shuttling of exosomal miR-7 to EOC cells, thereby inhibiting the EGFR/AKT/ERK1/2 pathway. (C) 2017 Elsevier B.V. All rights reserved.
机译：Exosomal-miRNA被涌现为肿瘤细胞和巨噬细胞之间的串扰的介质。在这项研究中，我们观察到衍生自调节刺激的巨噬细胞（TMS）的外泌体可以通过上皮卵巢癌（EOC）细胞内化并抑制细胞转移。通过miRNA微阵列分析，我们确定了19个miRNA，其在衍生自巨噬细胞的外泌体中差异表达，所述巨噬细胞源于或不调整。该研究验证，调整不仅增加了巨噬细胞和其分泌的外泌体在巨噬细胞和其分泌的外泌体的水平，而且导致受体EOC细胞中的miR-7水平升高，这最终降低了EGFR /的活动AKT / ERK1 / 2路径。在TMS中的抗血清蓟-7的预染色显着降低了巨噬细胞的miR-7的水平，其分泌的外泌体和受体EoC细胞随着EoC转移的增强，表明Exosomal miR-7的参与调节转移中的TMS EOC细胞。最后，来自TMS的外来体显着阻断了异种移植小鼠模型中的EOC转移。这些发现提供了一种新的模型，其中TMS通过穿梭于外泌体miR-7至EoC细胞抑制EoC细胞的转移，从而抑制EGFR / AKT / ERK1 / 2途径。 （c）2017 Elsevier B.v.保留所有权利。

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  • 来源
    《Cancer letters》 |2017年第2017期|共8页
  • 作者

    Hu Yuan; Li Dong; Wu Anyue; Qiu Xingdi; Di Wen; Huang Lei; Qiu Lihua;

  • 作者单位

    Shanghai jiao Tong Renji Hosp Sch Med Dept Gynecol &

    Obstet Shanghai 200127 Peoples R China;

    Shanghai jiao Tong Renji Hosp Sch Med Dept Gynecol &

    Obstet Shanghai 200127 Peoples R China;

    Shanghai jiao Tong Renji Hosp Sch Med Dept Gynecol &

    Obstet Shanghai 200127 Peoples R China;

    Shanghai jiao Tong Renji Hosp Sch Med Dept Gynecol &

    Obstet Shanghai 200127 Peoples R China;

    Shanghai jiao Tong Renji Hosp Sch Med Dept Gynecol &

    Obstet Shanghai 200127 Peoples R China;

    Shanghai Jiao Tong Univ Sch Med Dept Pathophysiol Key Lab Cell Differentiat &

    Apoptosis Minist;

    Shanghai jiao Tong Renji Hosp Sch Med Dept Gynecol &

    Obstet Shanghai 200127 Peoples R China;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 肿瘤学;
  • 关键词

    Exosomes; MiR-7; TWEAK; Macrophages; Metastasis; Epithelial ovarian cancer;

    机译：外泌体;miR-7;调整;巨噬细胞;转移;上皮卵巢癌;

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