Fig. 6
SMAD3-containing exosomes increase in HCC patients’ sera and correlate with the clinicopathology of HCC patients. a The level of SMAD3 protein in the serum exosomes derived from healthy donors and patients was determined by ELISA. b, c The SMAD3 level in HCC patients’ serum exosomes was correlated with disease stage and pathological grade. d Grouping of 24 HCC patients cutoff by the median value (1523 pg/ml). e Disease-free survival of HCC patients with high (n = 12) or low (n = 12) SMAD3 levels in serum exosomes was estimated using the Kaplan–Meier method. f The expression of SMAD3 was determined in HCC tissue. Representative images are shown from four patients with low and high SMAD3 levels in serum exosomes. Statistic analysis of SMAD3 concentration in serum exosomes vs. in HCC tissues was shown (n = 11). g The receiver operating characteristic (ROC) curve of AFP and/or exosomes-containing SMAD3 for HCC diagnosis. HCC group (n = 29), Control group (n = 37). h A scheme showing that PTDEs promote lung metastasis by enhancing adhesion of CTCs. Primary HCC lesions release PTDEs containing both mRNA and protein of SMAD3. The SMAD3-containing PTDEs deliver the bioactive materials including the SMAD3 mRNA and protein to CTCs in the circulation. Enhanced SMAD3 signaling induces a higher level of ROS in CTCs. The adhesive capacity of CTCs is upregulated by increased ROS, and thus more CTCs can extravasate to form metastases in the lung
