Qu,Zhen, Feng,Jiawei, Pan,Hua, Jiang,Yong, Duan,Yunfei, and Fa,Zhenzhong
Zhen Qu,1,* Jiawei Feng,1,* Hua Pan,2 Yong Jiang,1 Yunfei Duan,1 Zhenzhong Fa31Department of Hepatopancreatobiliary Surgery, The First People’s Hospital of Changzhou, the Third Hospital Affiliated to Soochow University, Changzhou, Jiangsu, People’s Republic of China; 2Department of Hepatobiliary Surgery, The People’s Hospital of Liyang, Liyang, Jiangsu, People’s Republic of China; 3Department of Hepatobiliary Surgery, Changzhou Wujin People’s Hospital, Wujin Hospital Affiliated to Jiangsu University, Changzhou, Jiangsu, People’s Republic of ChinaCorrespondence: Yunfei DuanDepartment of Hepatopancreatobiliary Surgery, The First People’s Hospital of Changzhou, The Third Hospital Affiliated to Soochow University, Changzhou, Jiangsu, People’s Republic of ChinaEmail 605035098@qq.comZhenzhong FaDepartment of Hepatobiliary Surgery, Changzhou Wujin People’s Hospital, Wujin Hospital Affiliated to Jiangsu University, Changzhou, Jiangsu, People’s Republic of ChinaEmail wjphfzz@126.com*These authors contributed equally to this workBackground: Exosomes are nano-sized biological vesicles released by many kinds of cells, which play an important role in tumor metastasis through transporting cytokines, RNAs and proteins. However, the molecular mechanisms of exosomes in hepatocellular carcinoma (HCC) metastasis are not completely understood.Materials and methods: Exosomes derived from hepatoma cell lines with different invasion characteristics. Exosome characteristics, cell migration and invasion, and effects on major signal transduction pathways deregulated in cancer cells were analyzed by transmission electron microscopy (TEM), wound-healing assay, Trans-well invasion assay and Western blot-based assays, respectively. Moreover, exosomes effects on tumor metastasis in vivo were investigated by subcutaneous transplantation tumor model of athymic nude mice.Results: Exosomes derived from hepatoma cells can promote the migration and invasion of recipient cells, induce the decrease of E-cadherin expression, increase the expression of Vimentin and promote epithelial-mesenchymal transition (EMT) in cells. Moreover, highly invasive hepatoma-cells-derived exosomes effects are stronger than low-invasive hepatoma cells and normal liver cells exosomes. Mechanistic studies showed that the biological alterations in recipient HCC cells treated with MHCC97H and MHCC97L-derived exosomes were caused by inducing EMT via TGF-β/Smad signaling pathway. In vivo experiments also suggest that highly invasive hepatoma cells derived exosomes are more likely to promote lung metastasis of HCC in nude mice.Conclusion: Our results reveal the important role of tumor-derived exosomes in the migration and invasion of recipient cells and exosomes may be the novel therapeutic and prognostic targets for HCC patients.Keywords: HCC, exosomal, TGF-β, EMT, tumor metastasis