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Table 1 The roles of exosomes within TME in HCC development and progression

From: Exosome-mediated communication in the tumor microenvironment contributes to hepatocellular carcinoma development and progression

Exosomal cargos Regulation Biological function Mechanism Reference
14-3-3ζ Increased Impair antitumor function Inhibit the antitumor functions of TILs and the vitality and proliferation of peripheral blood CD3+ T cells [55]
MICA*008 Increased Impair cytotoxic function Induce NKG2D downregulation on NK cell surface [58]
HCC antigens Increased Promote immune responses Activate immune response mediated by DCs [59]
Not mentioned Unvaried Regulate immunosuppression Alter the immunosuppressive status through STAT3 pathway in macrophages [62]
miR-490 Increased Inhibit metastasis Mast cells are stimulated by HCV-E2 and secrete exosomes to inhibit the ERK1/2 pathway [63]
miR-142, miR-223 Increased Inhibit proliferation Decrease reporter protein expression and endogenously express stathmin-1 and insulin-like growth factor-1 receptor [64]
linc-RoR Increased Regulate energy metabolism Activate microRNA-145/HIF-1α/PDK1 pathway and enhance the glycolysis process [65]
   Induce chemoresistance Activate TGF-β signaling and promote colony formation of CD133+ T-IC [66]
miRNA Increased Promote migration and invasion Induce TGF-β and TAK1 expression [12]
miR-155 Increased Promote formation and development Promote inflammation and positively correlate with IL-6 or IL-8 levels [67]
miR-1247-3p Increased Promote metastasis Target B4GALT3 and activate β1-integrin–NF-κB pathway [50]
miR-30a Decreased Promote proliferation and metastasis Mediate Beclin 1 and Atg5-dependent autophagy [68]
miR-320a Decreased Promote metastasis Target PBX3 and MAPK pathway, induce EMT, and upregulate CDK2 and MMP-2 expression [69]
miR-122 Decreased Promote proliferation IGF1 prevents intercellular exosomal transfer of miR-122 [70]
  Increase Induce chemosensitivity Induce chemosensitivity (5-FU and sorafenib) [71]
miR-9-3p Decreased Promote proliferation Regulate HBGF-5 and ERK1/2 expression [72]
VASN Increased Promote HUVECs cells migration Not mentioned [73]
RNAs, miRNAs Polytropic Associated with the degree of lumen formation Not mentioned [74]
miR-210-3p Increased Increase angiogenesis Inhibit the expression of SMAD4 and STAT6 in ECs [75]
lincRNA H19 Increased Increase angiogenesis Increase VEGF release and the production of VEGF-R1 [76]
miR-221 Increased Increase angiogenesis Activate SAND/NF-κB pathway and upregulate CXCL16 expression [77, 78]
miR-21 Increased Increase angiogenesis Activate the STAT3/VEGF pathway [77, 79]
Not mentioned Not mentioned Induce chemoresistance Activate HGF/c-Met/Akt pathways and restrain apoptosis [80]
Fibronectin1 COL2A1, FGG Increased Promote metastasis Induce either partial or total EMT [81]
RNAs, proteins Polytropic Promote migration and invasion Activate PI3K/AKT and MAPK pathways in MIHA and increase MMP-2 and MMP-9 secretion [82]
miR-103 Increased Promote metastasis Inhibit the expression of VE-Cad, p120, and ZO-1 [83]
AFP Increased Promote immune responses; Inhibit proliferation Enhance CD8+ T lymphocytes response, improve IFN-γ and IL-2 expression [84]
HSP Increased Promote immune responses Improve tumor immunogenicity and induce NK cell responses [85]
PD-L1 Increased Promote proliferation Suppress T cell activation in the draining lymph node [86]
miR-26a Increased Inhibit proliferation Bind to HepG2 cells via the scavenger receptor class B type 1-Apo-A1 complex [87]
Doxorubicin Increased Inhibit proliferation imDCs were engineered to express Lamp2b fused with v integrin-specific iRGD peptide [88]
lincRNA-VLDLR Increased Induce chemoresistance Increase ABCG2 expression and restrain apoptosis [89]