The Role of Exosomes in the Crosstalk between Adipocytes and Liver Cancer Cells
Abstract
:1. Introduction
2. Adipogenesis and Adipocytes
3. Adipocytes and the Tumor Microenvironment
4. Exosomes
4.1. Exosome Biosynthesis
4.2. Exosome Secretion and Cell Signaling
5. Adipocyte-Derived Exosomes (AdExos)
5.1. AdExos miRNAs and Chronic Inflammation
5.2. AdExos Carriers and Lipolysis
5.3. AdExos Carriers and Tumorigenesis
6. AdExos Mediated Cell Signaling Progression in HCC
7. HCCExos Mediated Cell Signaling and Progression in HCC
8. Exosomes as Therapeutic Vehicles
9. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
HCC | hepatocellular carcinoma |
NAFLD | non-alcoholic fatty liver disease |
AFLD | alcoholic fatty liver disease |
AdExos | adipocyte-derived exosomes |
HCCExos | HCC-derived exosomes |
SCs-AdExos | exosomes from adipose-derived stem cells |
MSCs-AdExos | exosomes from adipocyte-derived mesenchymal stem cells |
HBV | hepatitis B virus |
HCV | hepatitis C virus |
TGF-β | transforming growth factor-β |
VEGFs | vascular endothelial growth factors |
KLF4 | Krupel-like factor 4 |
WAT | White adipose tissue |
BAT | Brown adipose tissue |
UCP1 | uncoupling protein-1 |
CAAS | cancer-associated adipocyte |
MCP | monocyte chemoattractant protein |
CAFs | cancer-associated fibroblasts |
ECM | extracellular matrix |
EMT | epithelial to mesenchymal transition |
EVs | extracellular vesicles |
mRNA | messenger RNA |
miRNA | microRNA |
lncRNA | long non-coding RNA |
circRNA | circular RNA |
DNA | deoxyribonucleic acid |
ESCRT | endosomal sorting complex required for transport |
TSG101 | tumor suppressor susceptibility gene 101 |
CHMP4 | charged multivesicular protein body 4 |
VPS-4 | vacuolar protein sorting 4 |
MVBs | microvesicular bodies |
ILVs | Intraluminal Vesicles |
ACVR2B | activin receptor type-2B |
IBD | inflammatory bowel disease |
VEGF-C | vascular endothelial growth factor-C |
ARG-1 | arginase-1 |
IL-10 | interleukin-10 |
Gce1 | glycosylphosphatidylinositol-anchored (c)AMP-degrading phosphodiesterase |
VHL | Von Hippel–Lindau |
circ-BD | circRNA that regulate deubiquination |
USP7 | Ubiquitin-specific protease 7 |
VHL | von Hippel–Lindau |
NKT-cell | natural killer T-cell |
ADC | apparent diffusion coefficient |
HST-T6 | hepatic stellate; |
TAK1 | transforming growth factor β activated kinase-1 |
JNK | c-Jun NH2-terminal kinase |
NF | nuclear factor |
HUVECs | human umbilical vein endothelial cells |
B4GALT3 | β-1,4-galactosyltransferases |
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Exosome Source | Exosomal Cargo | Cell Signaling and Biological Function in Human Disease | Ref No. |
---|---|---|---|
AdExos | miRNA-23b, miRNA-148b, miRNA-4269, miRNA-4429 | AdExos from obese patients downregulates ACVR2B and regulates TGF-β1/Wnt/β signaling in A549 cells. | [64] |
AdExos | miRNA-148b, and miRNA-4269, miRNA-23b and miRNA-4429 | AdExos from visceral adipocyte tissue dysregulates TGF-β family members in hepatic stellate cells and HCC HepG2 cells. | [65] |
AdExos | miRNA-132 | EdExos from VEGFC/adipocyte derived stem cells increased proliferation/migration/tube formation and lymphangiogenesis by targeting Smad-7 and regulating TGF-β/Smad signaling. | [66] |
AdExos | miRNA-34a | Incubation of AdExos with bone marrow-derived macrophages inhibited IL-4-induced M2 macrophage polarization by directly targeting Krüppel-like factor 4 (Klf4). | [68] |
AdExos | miRNA-155 | HFD increased accumulation of AdExos miRNA-155 and polarization of M1 macrophages led to increased inflammation and insulin resistance in obese mice. | [69,70] |
AdExos | Gce1, 5′-nuceotidase CD73 | Gce1 and CD73 are released from adiposomes to intracellular lipid droplets of the acceptor adipocytes upregulates esterification of fatty acids into triacylglycerol. | [71] |
AdExos | Neutral lipids | Obese mice released more exosomes than lean mice. These exosomes provided precursor lipids such as acylglyceride, inducing the differentiation of bone marrow progenitors into adipose tissue macrophages-like cells. | [59] |
AdExos | MMP3 | AdExos from 3T3-L1 increased MMP9 activity and metastasis in 3LL lung cancer cells. | [72] |
AdExos | Variety of proteins | Exposure of AdExos isolated from obese individuals or from 3T3-F442A cells regulates migration/invasion through metabolic programming in SKMEL28 and 1205Lu melanomas. | [73] |
MSCs-AdExos | 1185 protein groups | MSCs-AdExos cargo can regulate metabolism, motility, tissue repair, protein turnover, chaperoning and post transcriptional modifications. | [74] |
AdExos (pre-adipocytes) | miRNA-140, SOX9 and other oncogenic growth factors and cytokines | AdExos increased migration/proliferation/mamosphere formation and breast cancer tumor growth in vivo. | [75] |
MSCs-AdExos | Not specified | MSCs-AdExos increased proliferation/migration by activation of the Wnt signaling pathway in MCF7 breast cancer cells. | [76] |
MSCs-AdExos | miRNA-4792, miRNA-320b, miRNA-320a and other miRNAs | MSCs-AdExos decreased proliferation/wound-repair/colony formation by increasing apoptosis in ovarian cancer cells. | [77] |
AdExos | miRNA-23a/b | Treatment of various HCC cell lines with ADExos promoted tumor growth in vivo by downregulation of VHL. | [78] |
AdExos | circ-BD (circRNA) | Higher levels of circ-DB in AdExos from obese HCC patients correlate with a decreased in miRNA-34a, activation of USP7/Cyclin A2 signaling led to increased HCC aggressiveness. | [79] |
HCCExos | Various proteins | HCCExos internalized by adipocytes resulting in increased inflammatory cytokine secretion, NF-κB signaling, proliferation/migration, and tumor growth in vivo. | [80] |
HCCExos | miRNAs | HCCExos promotes inter-cellular communication and aggressiveness by TAK1 expression and by modulation of JNK/p38 MAPK and NF-κB signaling pathways. | [81] |
HCCExos | MET protooncogene, S100 family members and caveolins | Exposure of HCCExos to non-motile MIHA cells activated PI3K/AKT/MAPK signaling, increased secretion of MMP-2 and MMP-9, and lead to increased migration/invasion and motility. | [82] |
HCCExos | lncRNA H19 | HCCExos from Huh7-CD90+ cells promoted transcription of VEGF, angiogenesis and cell adhesion in HUVECs. | [83] |
HCCExos | Pro-tumorigenic RNAs and proteins | HCCExos from highly metastatic HCC MHCC97H cells increased migration/chemotaxis and EMT through the MAPK/ERK signaling in low metastatic HCC cells | [84] |
HCCExos | miRNA-1247-3p | HCCExos from highly metastatic HCC cells promoted the conversion of fibroblasts into cancer-associated fibroblasts and secretion of inflammatory cytokine by targeting B4GALT3 and activating β1-integrin-NF-κB signaling. | [85] |
HCCExos | miRNA-122 | HCCExos from Huh7 reduced cell proliferation and cell growth in HepG2 HCC cells. | [86] |
HCCExos | lncRNA TUC339 | HCCExos promoted HCC cell growth and adhesion by modulating local tumor environment. | [87] |
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Rios-Colon, L.; Arthur, E.; Niture, S.; Qi, Q.; Moore, J.T.; Kumar, D. The Role of Exosomes in the Crosstalk between Adipocytes and Liver Cancer Cells. Cells 2020, 9, 1988. https://doi.org/10.3390/cells9091988
Rios-Colon L, Arthur E, Niture S, Qi Q, Moore JT, Kumar D. The Role of Exosomes in the Crosstalk between Adipocytes and Liver Cancer Cells. Cells. 2020; 9(9):1988. https://doi.org/10.3390/cells9091988
Chicago/Turabian StyleRios-Colon, Leslimar, Elena Arthur, Suryakant Niture, Qi Qi, John T. Moore, and Deepak Kumar. 2020. "The Role of Exosomes in the Crosstalk between Adipocytes and Liver Cancer Cells" Cells 9, no. 9: 1988. https://doi.org/10.3390/cells9091988