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Tumor-derived exosomes promote tumor self-seeding in hepatocellular carcinoma by transferring miRNA-25-5p to enhance cell motility

Oncogene volume 37, pages 4964–4978 (2018)Cite this article

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Abstract

Tumor self-seeding occurs when circulating malignant cells reinfiltrate the original tumor. The process may breed more aggressive tumor cells, which may contribute to cancer progression. In this study, we observed tumor self-seeding in mouse xenograft models of hepatocellular carcinoma (HCC) for the first time. We confirmed that circulating tumor cell uptake of tumor-derived exosomes, which are increasingly recognized as key instigators of cancer progression by facilitating cell–cell communication, promoted tumor self-seeding by enhancing the invasive and migration capability of recipient HCC cells. Horizontal transfer of exosomal microRNA-25-5p to anoikis-resistant HCC cells significantly enhanced their migratory and invasive abilities, whereas inhibiting microRNA-25-5p alleviated these effects. Our experiments delineate an exosome-based novel pathway employed by functional microRNA from the original tumor cells that can influence the biological fate of circulating tumor cells.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81472212), 973 Program of China (No. 2014CB542101), Key Program of Medical Scientific Research Foundation of Zhejiang Province, China (No.WKJ-ZJ-1410), Key Program of Administration of Traditional Chinese Medicine of Zhejiang Province, China (No.2014ZZ007) and Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents.

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Authors and Affiliations

  1. Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    Hao Liu, Wei Chen, Xiao Zhi, En-Jiang Chen, Tao Wei, Jian Zhang, Jian Shen, Li-Qiang Hu, Xue-Li Bai & Ting-Bo Liang

  2. Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China

    Hao Liu, Wei Chen, Xiao Zhi, En-Jiang Chen, Tao Wei, Jian Zhang, Jian Shen, Li-Qiang Hu, Xue-Li Bai & Ting-Bo Liang

  3. Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, China

    Bin Zhao & Xin-Hua Feng

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Liu, H., Chen, W., Zhi, X. et al. Tumor-derived exosomes promote tumor self-seeding in hepatocellular carcinoma by transferring miRNA-25-5p to enhance cell motility. Oncogene 37, 4964–4978 (2018). https://doi.org/10.1038/s41388-018-0309-x

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