Non-Parenchymal Cells and the Extracellular Matrix in Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease
Abstract
:Simple Summary
Abstract
1. Introduction
2. Hepatocyte Injury in HCC Pathogenesis: A Brief Summary
3. Inflammatory Pathways in the Pathogenesis of NAFLD and NAFLD-Related HCC
3.1. M1-Type Macrophages Drive Inflammation and Subsequent Hepatocarcinogenesis
3.2. Pro-Carcinogenic M2-Type Macrophages
3.3. Switch from M1- to M2-Type Macrophages Stimulates Progression of NAFLD-Related HCC
3.4. Tumor-Associated Macrophages (TAMs)
4. Fibrogenesis
4.1. Matrix Stiffness Stimulates NAFLD-Related Hepatocarcinogenesis
4.2. Liver Sinusoidal Endothelial Cells (LSECs)
4.3. Angiogenesis
5. Immune Escape of Tumor Cells
5.1. Role of the Adaptive Immune System
5.2. CD8+ T Cells
5.3. CD4+ T Cells
5.4. Complex Interplay between the Innate and Adaptive Immune System
5.5. Immunotherapy for NAFLD-Related HCC
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
APC | Antigen-presenting cell |
CAF | Carcinoma-associated fibroblast |
DC | Dendritic cell |
ECM | Extracellular matrix |
eNOS | Endothelial nitric oxide synthase |
ERK | Extracellular signal-regulated kinase |
FABP | Fatty acid-binding protein |
FFA | Free fatty acid |
GM-CSF | Granulocyte-macrophage colony-stimulating factor |
HCC | Hepatocellular carcinoma |
HGF | Hepatocyte growth factor |
Hh | Hedgehog |
HIF | Hypoxia-inducible factor |
HSC | Hepatic stellate cell |
IFN | Interferon |
IGF | Insulin-like growth factor |
IL | Interleukin |
JAK | Janus kinase |
JNK | c-Jun N-terminal kinase |
KC | Kupffer cell |
LPS | Lipopolysaccharides |
LSEC | Liver sinusoidal endothelial cell |
MAPK | Mitogen-activated protein kinase |
M-CSF | Macrophage colony-stimulating factor |
MDSC | Myeloid-derived suppressor cell |
MMP | Matrix metalloproteinase |
NAFLD | Non-alcoholic fatty liver disease |
NASH | Non-alcoholic steatohepatitis |
NET | Neutrophil extracellular trap |
NF-κB | Nuclear factor kappa-light-chain-enhancer of activated B cells |
NK cell | Natural killer cell |
NKT cell | Natural killer T cell |
NOS | Nitric oxide synthase |
OA | Oleic acid |
OPN | Osteopontin |
PA | Palmitic acid |
PD | Programmed death |
PD-L | Programmed death ligand |
PI3K | Phosphoinositide-3 kinase |
PlGF | Placental growth factor |
PPAR | Peroxisome proliferator-activated receptor |
ROS | Reactive oxygen species |
SDF | Stromal-derived factor |
STAT | Signal transducer and activator of transcription |
TAM | Tumor-associated macrophage |
TAZ | Transcriptional coactivator with PDZ-binding motif |
TREM2 | Triggering receptor expressed on myeloid cells 2 |
TGF | Transforming growth factor |
Th | T helper |
TIL | Tumor-infiltrating lymphocyte |
TIMP | Tissue inhibitor of metalloproteinase |
TLR | Toll-like receptor |
TME | Tumor microenvironment |
TNF | Tumor necrosis factor |
TNSMF | Tumor necrosis superfamily member |
Treg cell | Regulatory T cell |
VAP | Vascular adhesion protein |
VEGF | Vascular-endothelial growth factor |
Wnt | Wingless-related integration sight |
YAP | Yes-associated protein |
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van Son, K.C.; Verschuren, L.; Hanemaaijer, R.; Reeves, H.; Takkenberg, R.B.; Drenth, J.P.H.; Tushuizen, M.E.; Holleboom, A.G. Non-Parenchymal Cells and the Extracellular Matrix in Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease. Cancers 2023, 15, 1308. https://doi.org/10.3390/cancers15041308
van Son KC, Verschuren L, Hanemaaijer R, Reeves H, Takkenberg RB, Drenth JPH, Tushuizen ME, Holleboom AG. Non-Parenchymal Cells and the Extracellular Matrix in Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease. Cancers. 2023; 15(4):1308. https://doi.org/10.3390/cancers15041308
Chicago/Turabian Stylevan Son, Koen C., Lars Verschuren, Roeland Hanemaaijer, Helen Reeves, R. Bart Takkenberg, Joost P. H. Drenth, Maarten E. Tushuizen, and Adriaan G. Holleboom. 2023. "Non-Parenchymal Cells and the Extracellular Matrix in Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease" Cancers 15, no. 4: 1308. https://doi.org/10.3390/cancers15041308