Cancer-Associated Fibroblasts in Cholangiocarcinoma: Current Knowledge and Possible Implications for Therapy
Abstract
:1. Introduction
2. Cancer-Associated Fibroblasts Origin and Phenotypic Subpopulations
3. Cancer-Associated Fibroblast Molecular Expression and Tumor Crosstalk
4. Cancer-Associated Fibroblasts and Prognosis Correlation
5. Cancer-Associated Fibroblasts and Potential Therapies
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Activated Pathways | Therapeutic Correlation | Prognostic Value | |
---|---|---|---|
IL-33 | promoting cell proliferation and extracellular matrix deposition | N/D | higher expression correlates with good prognosis |
SDF-1 | activation and proliferation of HSC; upregulate BCL-2, ERK-1/2, PI3K, and AKT pathways | N/D | higher expression correlates with poor prognosis |
POSTN | attract TAMs, enhances CCA cell invasion | N/D | expression correlates with shorter survival |
α-SMA | enhances cell growth and invasiveness | nintedanib suppresses CAF proliferation and α-SMA expression | negative prognostic factor |
PDGFR-D | induces fibroblast migration and stimulates VEGF-A/C production promoting lymphangiogenesis | imatinib has disappointing preliminary results | negative prognostic factor |
PlGF | promotes CAFs myofibroblast-like phenotype; activates AKT/NFkB pathway stimulating invasive growth of intrahepatic CCA | anti-PlGF therapy has antiangiogenic effect, decreases desmoplasia and hypoxia and increases overall survival | N/D |
HB-EGF | activation of STAT-3 promoting tumor cells migration, motility, and invasion | gefitinib has disappointing preliminary results | N/D |
BH 3-only protein | activation of Bcl-2 proteins, promoting apoptotic cell death | navitoclax induces selective apoptotic cell death in α-SMA+ CAFs, reducing tumor burden and metastasis with improved survival | N/D |
IL-6 | stimulation of Wnt pathway with activation of cadherin | resveratrol inhibits CAFs IL-6 production, reducing tumor invasiveness and metastatic potential | |
Podoplanin | promote tumor progression and lymph node metastasis | N/D |
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Montori, M.; Scorzoni, C.; Argenziano, M.E.; Balducci, D.; De Blasio, F.; Martini, F.; Buono, T.; Benedetti, A.; Marzioni, M.; Maroni, L. Cancer-Associated Fibroblasts in Cholangiocarcinoma: Current Knowledge and Possible Implications for Therapy. J. Clin. Med. 2022, 11, 6498. https://doi.org/10.3390/jcm11216498
Montori M, Scorzoni C, Argenziano ME, Balducci D, De Blasio F, Martini F, Buono T, Benedetti A, Marzioni M, Maroni L. Cancer-Associated Fibroblasts in Cholangiocarcinoma: Current Knowledge and Possible Implications for Therapy. Journal of Clinical Medicine. 2022; 11(21):6498. https://doi.org/10.3390/jcm11216498
Chicago/Turabian StyleMontori, Michele, Chiara Scorzoni, Maria Eva Argenziano, Daniele Balducci, Federico De Blasio, Francesco Martini, Tiziana Buono, Antonio Benedetti, Marco Marzioni, and Luca Maroni. 2022. "Cancer-Associated Fibroblasts in Cholangiocarcinoma: Current Knowledge and Possible Implications for Therapy" Journal of Clinical Medicine 11, no. 21: 6498. https://doi.org/10.3390/jcm11216498