Recreating Tumour Complexity in a Dish: Organoid Models to Study Liver Cancer Cells and their Extracellular Environment
Abstract
:1. Introduction
2. Limitations of Current in Vitro Cancer Models
2.1. Two-Dimensional Cell Line Models
2.2. Three-Dimensional Liver Cancer Models
2.2.1. Scaffold-Based Models
2.2.2. Scaffold-Free Models
3. Emerging Organoid Models
3.1. Organoid Culture Systems
3.2. Primary Liver Cancer (PLC) Organoids
3.3. Current Limitations of Organoid Models
4. The Liver Cancer Extracellular Environment
4.1. Role of the Extracellular Environment in Hepatocellular Carcinoma
4.2. Role of the Extracellular Environment in Cholangiocarcinoma
5. Adapting Organoid Models to Study Liver Cancer Cell Interactions with the Extracellular Environment
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
PLC | Primary liver cancer |
CCA | Cholangiocarcinoma |
iCCA | Intrahepatic cholangiocarcinoma |
pCCA | Perihilar cholangiocarcinoma |
dCCA | Distal cholangiocarcinoma |
CAF | Cancer-associated fibroblast |
ECM | Extracellular matrix |
PVA | Poly(vinyl alcohol) |
RWV | Rotary wall vessel |
LGR5 | Leucine-rich repeat-containing G-protein coupled receptor 5 |
KRAS | Ki-ras |
Pik3ca | Phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha |
FGFR2-AHCYL1 | Fibroblast growth factor receptor 2-adenosylhomocysteinase like 1 |
PEG | Polyethylene glycol |
MMP | Matrix metallopeptidases |
TME | Tumour microenvironment |
PVTT | Portal vein tumour thrombus |
EMT | Epithelial-to-mesenchymal transition |
TEE | Tumour extracellular environment |
LOXL2 | Lysyl oxidase like 2 |
YAP | Yes-associated protein |
TAZ | Transcriptional co-activator with PDZ-binding motif |
PDAC | Pancreatic ductal adenocarcinoma |
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Comparison | 2D Cell Lines | Spheroids | Organoids |
---|---|---|---|
Origin of cells | Immortalized cell lines | Often immortalized cell lines or tumour biopsies | Tissue-specific stem cells |
Morphology | Sheet-like flat monolayer | Cell-clusters within 3D environment | Self-organizing, mimicking organ structure |
Drug sensitivity | Very effective due to 2D morphology | More resistant compared to 2D, better in vivo drug response predictor | Patient-specific responses and matched controls for personalized therapy and best in vivo drug response predictor |
Throughput drug screening | Suitable for high-throughput screening | Less suitable for high-throughput drug screening | Less suitable for high-throughput drug screening |
Resource costs | Low | Medium | Medium-high |
Heterogeneity | Cell-line derived from a single cell | Related to initial cell population | Related to patient used for cell isolation |
In vivo features | Cellular properties | Cell-cell interactions, hypoxia, drug penetration, production of ECM | Cell-cell interactions, mutational landscape of original tumour, cellular heterogeneity |
Long-term expansion | Immortalized for easy expansion | In few cases long-term reported, loss of heterogeneity | Robust long-term expansion with maintenance of heterogeneity |
(Bio)materials for culture | Plastic or biomaterial coatings | Wide variety of (bio) materials | Primarily Matrigel/BME |
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van Tienderen, G.S.; Groot Koerkamp, B.; IJzermans, J.N.M.; van der Laan, L.J.W.; Verstegen, M.M.A. Recreating Tumour Complexity in a Dish: Organoid Models to Study Liver Cancer Cells and their Extracellular Environment. Cancers 2019, 11, 1706. https://doi.org/10.3390/cancers11111706
van Tienderen GS, Groot Koerkamp B, IJzermans JNM, van der Laan LJW, Verstegen MMA. Recreating Tumour Complexity in a Dish: Organoid Models to Study Liver Cancer Cells and their Extracellular Environment. Cancers. 2019; 11(11):1706. https://doi.org/10.3390/cancers11111706
Chicago/Turabian Stylevan Tienderen, Gilles S., Bas Groot Koerkamp, Jan N. M. IJzermans, Luc J. W. van der Laan, and Monique M. A. Verstegen. 2019. "Recreating Tumour Complexity in a Dish: Organoid Models to Study Liver Cancer Cells and their Extracellular Environment" Cancers 11, no. 11: 1706. https://doi.org/10.3390/cancers11111706
APA Stylevan Tienderen, G. S., Groot Koerkamp, B., IJzermans, J. N. M., van der Laan, L. J. W., & Verstegen, M. M. A. (2019). Recreating Tumour Complexity in a Dish: Organoid Models to Study Liver Cancer Cells and their Extracellular Environment. Cancers, 11(11), 1706. https://doi.org/10.3390/cancers11111706