Exosomal IGFBP2 derived from highly metastatic promotes hepatocellular carcinoma metastasis by inducing epithelial...

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.