Yu Zeqian, Zhao Susu, Ren Long, Wang Lishan, Chen Zhangjun, Hoffman Robert M, Zhou Jiahua
Department of Hepatic-Biliary-Pancreatic Center, Zhongda Hospital, Southeast University, Nanjing, China.
Department of Hepatobiliary Surgery Research Institute, Southeast University, Nanjing, China.
Oncotarget. 2017 Jun 28;8(38):63461-63483. doi: 10.18632/oncotarget.18831. eCollection 2017 Sep 8.
Exosomes play important roles in cell-cell communication, and are likely mediators of the metastatic cascade in cancer. This study examined the role of exosomes in pancreatic cancer cell adhesion, migration, and invasion. We isolated and purified exosomes from two isogenic pancreatic cancer cell lines with different metastatic potentials. Uptake of exosomes from highly metastatic Panc02-H7 cells decreased adhesion and increased migration and invasion capacity in weakly metastatic Panc02 cells . Exosomes from highly metastatic pancreatic cancer cells induced liver pre-metastatic niche formation in naïve mice and promoted primary tumor growth and liver metastasis . We identified 4,517 proteins in exosomes from Panc02 and Panc02-H7 cells via iTRAQ quantitative proteomic analyses, 79 of which were differentially expressed between the two cell lines. Bioinformatics analyses showed that most of the differentially expressed proteins were involved in pancreatic cancer growth, invasion, and metastasis, and that metabolism-related signaling pathways were involved in exosome-mediated intracellular communication. Further studies will be needed to determine whether these proteins are potential pancreatic cancer diagnostic/prognostic markers or novel therapeutic targets.
外泌体在细胞间通讯中发挥着重要作用，并且很可能是癌症转移级联反应的介导者。本研究检测了外泌体在胰腺癌细胞黏附、迁移和侵袭中的作用。我们从具有不同转移潜能的两种同基因胰腺癌细胞系中分离并纯化了外泌体。摄取来自高转移性Panc02-H7细胞的外泌体可降低低转移性Panc02细胞的黏附能力，并增加其迁移和侵袭能力。来自高转移性胰腺癌细胞的外泌体可在未经处理的小鼠中诱导肝脏前转移微环境的形成，并促进原发性肿瘤生长和肝转移。通过iTRAQ定量蛋白质组学分析，我们鉴定了Panc02和Panc02-H7细胞外泌体中的4517种蛋白质，其中79种在两种细胞系之间存在差异表达。生物信息学分析表明，大多数差异表达的蛋白质都参与了胰腺癌的生长、侵袭和转移，并且代谢相关信号通路参与了外泌体介导的细胞内通讯。还需要进一步研究以确定这些蛋白质是否为潜在的胰腺癌诊断/预后标志物或新型治疗靶点。
