title: The role of extracellular vesicles in mediating progression, metastasis and potential treatment of hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Department of Infection and Liver Diseases, Ningbo First Hospital, Ningbo, China.
authors.forename: Naibin
authors.initials: N
authors.lastname: Yang
authors.affiliation: Department of Infection and Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Institute of Liver Research, Wenzhou Medical University, Wenzhou, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Infection and Liver Diseases, Ningbo First Hospital, Ningbo, China.
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Infection and Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Institute of Liver Research, Wenzhou Medical University, Wenzhou, China.
authors.forename: Shengguo
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Infection and Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Institute of Liver Research, Wenzhou Medical University, Wenzhou, China.
authors.forename: Xinyue
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Infection and Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Institute of Liver Research, Wenzhou Medical University, Wenzhou, China.
authors.forename: Shunlan
authors.initials: S
authors.lastname: Ni
authors.affiliation: Department of The First Clinical Medical, Wenzhou Medical University, Wenzhou, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Jian
authors.affiliation: Department of Respiration, Lishui People's Hospital of Wenzhou Medical University, Lishui, China.
authors.forename: Cunlai
authors.initials: C
authors.lastname: Xu
authors.affiliation: Laboratory Animal Center, Wenzhou Medical University, Wenzhou, China.
authors.forename: Jiayin
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Infection and Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Institute of Liver Research, Wenzhou Medical University, Wenzhou, China.
authors.forename: Mingqin
authors.initials: M
authors.lastname: Lu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D055252:Cell-Derived Microparticles / Q000378:metabolism; D018281:Cholangiocarcinoma; D018450:Disease Progression; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D055354:Exosomes / Q000378:metabolism*; D000067128:Extracellular Vesicles / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D009362:Neoplasm Metastasis; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents
keywords: MSCs; exosomes; extracellular vesicles; hepatocellular carcinoma; miRNA