Exosomes derived from bone marrow mesenchymal stem cells promote osteosarcoma development by activating oncogenic autophagy

Exosomes derived from bone marrow mesenchymal stem cells promote osteosarcoma development by activating oncogenic autophagy
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骨髓间充质干细胞来源的外切体通过激活致癌自噬促进骨肉瘤的发展

DOI:
10.1016/j.jbo.2020.100280
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发表时间:
2020-04-01
影响因子:
3.4
通讯作者:
Sun, Luning
Sun, Luning
中科院分区:
医学2区
文献类型:
--
作者:
Huang, Yao;Liu, Wei;Sun, Luning

文献摘要

被引文献

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骨肉瘤是一种好发于青少年的恶性骨肿瘤。其肺转移率和死亡率高。以往的研究表明,人骨髓间充质干细胞(hBMSCs)可以促进包括骨肉瘤在内的多种肿瘤的恶性进展。同时,人们认识到来源于hBMSCs的外泌体(hBMSC-Exos)介导细胞间通讯,并在多种肿瘤的发生发展中表现出相似的作用。然而,hBMSC-Exos在OS发生发展中的作用仍不清楚,其潜在机制需要阐明。我们的研究结果表明,hBMSC衍生的外泌体促进OS细胞增殖,迁移和侵袭。同时,在OS细胞中沉默自噬相关基因5(ATG 5)消除了hBMSC-Exos在体外和体内的促肿瘤作用。我们目前的研究表明,hBMSC-Exos通过促进OS中的致癌性自噬来促进肿瘤的发生和转移。
Osteosarcoma (OS) is a malignant bone tumor that frequently occurs in adolescents. It has a high rate of pulmonary metastasis and mortality. Previous studies have demonstrated that human bone marrow mesenchymal stem cells (hBMSCs) can promote the malignant progression in various tumors, including OS. Also, it is recognized that exosomes derived from hBMSCs (hBMSC-Exos) mediate cell-to-cell communication and exhibit similar effects on the development of various tumors. However, the role of hBMSC-Exos in the development of OS is still unclear and the underlying mechanism needs to be elucidated. Our results show that hBMSC-derived exosomes promote OS cell proliferation, migration, and invasion. Meanwhile, silencing autophagy-related gene 5 (ATG5) in OS cells abolishes the pro-tumor effects of hBMSC-Exos in vitro and in vivo. Our present study demonstrates that hBMSC-Exos promotes tumorigenesis and metastasis by promoting oncogenic autophagy in OS.