The role of extracellular vesicles in mediating progression, metastasis and potential treatment of hepatocellular carcinoma

Naibin Yang, Shanshan Li, Guoxiang Li, Shengguo Zhang, Xinyue Tang, Shunlan Ni, Xiaomin Jian, Cunlai Xu, Jiayin Zhu and Mingqin Lu _

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Oncotarget. 2017; 8:3683-3695. https://doi.org/10.18632/oncotarget.12465

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Naibin Yang1, Shanshan Li2, Guoxiang Li1, Shengguo Zhang2, Xinyue Tang2, Shunlan Ni2, Xiaomin Jian3, Cunlai Xu4, Jiayin Zhu5 and Mingqin Lu2

1 Department of Infection and Liver Diseases, Ningbo First Hospital, Ningbo, China

2 Department of Infection and Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Institute of Liver Research, Wenzhou Medical University, Wenzhou, China

3 Department of The First Clinical Medical, Wenzhou Medical University, Wenzhou, China

4 Department of Respiration, Lishui People’s Hospital of Wenzhou Medical University, Lishui, China

5 Laboratory Animal Center, Wenzhou Medical University, Wenzhou, China

Correspondence to:

Mingqin Lu, email:

Keywords: extracellular vesicles, exosomes, miRNA, hepatocellular carcinoma, MSCs

Received: April 28, 2016 Accepted: September 28, 2016 Published: October 04, 2016


Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. As vectors for intercellular information exchange, the potential role of extracellular vesicles (EVs) in HCC formation, progression and therapy has been widely investigated. In this review, we explore the current status of the researches in this field. Altogether there is undeniable evidence that EVs play a crucial role in HCC development, metastasis. Moreover, EVs have shown great potential as drug delivery systems (DDSs) for the treatment of HCC. Exosomal miRNAs derived from HCC cells can enhance transformed cell growth in recipient cells by modulating the expression of transforming growth factor-β activated kinase-1(TAK1) and downstream signaling molecules. Furthermore, vacuolar protein sortin 4 homolog A(VPS4A) and insulin-like growth factor(IGF)-1 regulate exosome-mediated miRNAs transfer. Immune cells- derived EVs containing integrin αMβ2 or CD147 may facilitate HCC metastasis. In addition, EVs-mediated shuttle of long non-coding RNAs (lncRNAs), specifically linc- VLDLR and linc-ROR promote chemoresistance of malignant cells. Heat shock proteins (HSPs)-harboring exosomes derived from HCC tumor cells increase the antitumor effect of natural killer (NK) cells, thus enhancing HCC immunotherapy. Indeed, inhibition of HCC tumor growth has been associated with tumor cell-derived exosomes (TEX)-pulsed dentritic cells (DCs). Exosomes are also essential in liver metastasis during colorectal carcinoma (CRC) and pancreatic ductal adenocarcinomas (PDAC). Therefore, as nucleic acid and drug delivery vehicles, EVs show a tremendous potential for effective treatment against HCC.

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