The Role of Fibrosis and Liver-Associated Fibroblasts in the Pathogenesis of Hepatocellular Carcinoma
Abstract
1. Introduction
2. The Premalignant and Tumor Microenvironment in HCC
2.1. Premalignant Microenvironment in HCC
2.2. Tumor Microenvironment in HCC
3. Cancer-Associated Fibroblasts (CAFs)
3.1. Origin of CAFs
3.2. Markers of CAFs
3.3. CAFs in HCC
4. CAF-Dependent Mechanisms of Hepatocarcinogenesis
4.1. CAF-Dependent Alteration of ECM Promotes HCC
4.2. CAFs and Tumor Angiogenesis
4.3. CAF-Secreted Cytokines
4.4. CAFs and Immune Surveillance
4.5. CAFs and EMT
5. Conclusions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
HCC | Hepatocellular carcinoma |
HSCs | Hepatic stellate cells |
CAFs | Cancer-associated fibroblasts |
PFs | Portal fibroblasts |
ECM | Extracellular matrix |
EMT | Epithelial-mesenchymal transition |
PME | Premalignant microenvironment |
TME | Tumor microenvironment |
HBV | Hepatitis B virus |
HCV | Hepatitis C virus |
NAFLD | Non-alcoholic fatty liver disease |
α-SMA | Alpha-smooth muscle actin |
MMPs | Matrix metalloproteinases |
ROS | Reactive oxygen species |
TAMs | Tumor-associated macrophages |
NADPH | Nicotinamide adenine dinucleotide phosphate |
NOX1 | NADPH oxidase 1 |
CCl4 | Carbon tetrachloride |
BDL | Bile duct ligation |
FAP | Fibroblast activated protein |
NTF | Non-tumoral fibroblast |
VEGF | Vascular endothelial growth factor |
EGF | Epidermal growth factor |
DDRs | Discodin domain receptor |
PI3-K | phosphatidylinositol 3-kinase |
HGF | Hepatocyte growth factor |
CSC | Cancer-stem cell |
FAPα | Fibroblast activation protein α |
FSP-1 | Fibroblast specific protein 1 |
NG2 | Neuron-glial antigen-2 |
MFAP5 | Microfibril associated protein 5 |
Treg | Regulatory T cell |
MDSC | Myeloid derived suppressor cell |
DC | Dendritic cell |
NK | Natural killer |
CTLs | Cytotoxic T lymphocytes |
MSCs | Mesenchymal stem cells |
GFP | Green fluorescent protein |
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Baglieri, J.; Brenner, D.A.; Kisseleva, T. The Role of Fibrosis and Liver-Associated Fibroblasts in the Pathogenesis of Hepatocellular Carcinoma. Int. J. Mol. Sci. 2019, 20, 1723. https://doi.org/10.3390/ijms20071723
Baglieri J, Brenner DA, Kisseleva T. The Role of Fibrosis and Liver-Associated Fibroblasts in the Pathogenesis of Hepatocellular Carcinoma. International Journal of Molecular Sciences. 2019; 20(7):1723. https://doi.org/10.3390/ijms20071723
Chicago/Turabian StyleBaglieri, Jacopo, David A. Brenner, and Tatiana Kisseleva. 2019. "The Role of Fibrosis and Liver-Associated Fibroblasts in the Pathogenesis of Hepatocellular Carcinoma" International Journal of Molecular Sciences 20, no. 7: 1723. https://doi.org/10.3390/ijms20071723
APA StyleBaglieri, J., Brenner, D. A., & Kisseleva, T. (2019). The Role of Fibrosis and Liver-Associated Fibroblasts in the Pathogenesis of Hepatocellular Carcinoma. International Journal of Molecular Sciences, 20(7), 1723. https://doi.org/10.3390/ijms20071723