Liver cancer metastasis is the main cause of death in liver cancer patients. Exosomes, which are small vesicles released by cancer cells, play a crucial role in the metastasis of cancer. The aim of this study was to investigate the effect of exosomes derived from high metastatic potential liver cancer cells acting as cell to cell communication on liver cancer metastasis. Bioinformatics analysis was used to obtain the differential expression of exosomal mRNAs from the plasma of both liver cancer patients and healthy volunteers. Transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and protein blot were employed to characterize the exosomes. The molecular mechanisms and were explored by conducting CCK8, Transwell, Tunel, RTqPCR, western blot, and immunofluorescence staining. We examined IGFBP2 special expression in the plasma exosomes of both liver cancer patients and healthy volunteers, and its presence was associated with a poor prognosis in liver cancer patients. Furthermore, we observed that exosomes from highly metastatic liver cancer cells (MHCC97H) contained high levels of IGFBP2 and could enhance the metastatic potential of less aggressive liver cancer cells (Hep3B). Additionally, we discovered that IGFBP2 in MHCC97H-derived exosomes activated ERK signaling pathway, which triggered epithelial-mesenchymal transition (EMT) in Hep3B cells. Our study underscores the significance of exosomal IGFBP2 from highly metastatic liver cancer cells as a driver of metastasis in less invasive liver cancer cells. This suggests that targeting IGFBP2 in exosomes could be a promising strategy for the treatment and prognosis of liver cancer patients.

中文翻译：

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高转移性来源的外泌体IG​​FBP2通过诱导上皮间质转化促进肝细胞癌转移

肝癌转移是肝癌患者死亡的主要原因。外泌体是癌细胞释放的小囊泡，在癌症转移中发挥着至关重要的作用。本研究的目的是研究源自高转移潜力肝癌细胞的外泌体作为细胞间通讯对肝癌转移的影响。利用生物信息学分析获得肝癌患者和健康志愿者血浆中外泌体mRNA的差异表达。采用透射电子显微镜（TEM）、纳米颗粒跟踪分析（NTA）和蛋白质印迹来表征外泌体。通过CCK8、Transwell、Tunel、RTqPCR、蛋白质印迹和免疫荧光染色探讨其分子机制。我们检测了肝癌患者和健康志愿者血浆外泌体中IGFBP2的特殊表达，其存在与肝癌患者的不良预后相关。此外，我们观察到来自高度转移性肝癌细胞（MHCC97H）的外泌体含有高水平的IGFBP2，并且可以增强侵袭性较低的肝癌细胞（Hep3B）的转移潜力。此外，我们发现MHCC97H衍生的外泌体中的IGFBP2激活ERK信号通路，从而触发Hep3B细胞中的上皮间质转化（EMT）。我们的研究强调了高度转移性肝癌细胞的外泌体 IGFBP2 作为侵袭性较小的肝癌细胞转移驱动因素的重要性。这表明，靶向外泌体中的 IGFBP2 可能是肝癌患者治疗和预后的一种有前景的策略。