Modelling Cancer Pathophysiology: Mechanisms and Changes in the Extracellular Matrix During Cancer Initiation and Early Tumour Growth
Simple Summary
Abstract
1. Introduction
2. ECM Remodelling in Cancerogenic Environments
3. Epithelial Cellular Polarity and Early Tumorigenesis
3.1. Dysregulation in Cellular Polarity During Cancer Initiation and Early Tumorigenesis
3.2. In Vitro Models to Recapitulate Cell Polarity Dysregulations in Cancer
3.2.1. Advances in Hydrogel in Vitro Modelling to Study Cell Polarity
3.2.2. Alternative In Vitro Modelling Strategies of Cellular Polarity and Tumorigenesis
4. Cancer miRNAs and Their Impact on Tumour Initiation, Progression and ECM Remodelling
4.1. MicroRNA in Cancer and Cancer Models
Three-Dimensional In Vitro Models to Study MicroRNAs Associated with Cancer Initiation and Growth
5. EMT and EET in Tumour Initiation and Growth
5.1. The Role of EMT in Cancer Initiation and Early Tumour Growth
5.2. Development of EET to Support Tumorigenesis Under Hypoxic Environments
5.3. In Vitro Modelling Methods to Mimic Tumorigenic EMT and EET Processes
5.3.1. Three-Dimensional Modelling Platforms to Study EMT Mediation in Cancer
5.3.2. Three-Dimensional Modelling Platforms to Study EET and VM Processes
6. Vascularisation and Early Tumour Growth
6.1. Vasculogenesis in Cancer and Tumour Development
6.2. Angiogenesis in Cancer and Tumour Development
6.3. Vascularised In Vitro Models to Recapitulate Cancer Agiogenesis and Vasculogenesis
Method | Description | Advantages | Limitations | References |
---|---|---|---|---|
Matrigel™ Assays | Basement membrane extracts from Engelbreth-Holm-Swarm used to study vascular-like networks | - Easy to use and widely available - Allows rapid assessment of vascular-like network formation | - Lacks in vivo 3D cellular organisation - Its composition is undefined/heterogeneous, which can hinder reproducibility | [186,187,192] |
Hydrogel Models | Uses natural or synthetic polymers to form 3D hydrophilic ECM-like matrices | - Better mimics 3D architecture of ECM than Matrigel™ - Can incorporate well-defined chemical and mechanical factors to study vascularised cancer models | - Still lacks full complexity of in vivo settings - Difficulty in controlling the exact architecture of natural hydrogels - Some synthetic hydrogels may not fully support cellular functions | [189,193,194,195] |
Microfluidic Models | Use of organ-on-chip platforms to recreate vascularised tumour microenvironments | - Enables dynamic control of fluids, nutrients, and signalling molecules via perfusion mechanics - Precise control of microenvironments and perfusion systems | - Often simpler vascular architectures than those observed in vivo - Achieving physiologically relevant conditions can be challenging | [24,196,197] |
3D Bioprinting | Uses bioinks to spatially organised cells and fabricate complex vascularised constructs | - Precise spatial control of cells and scaffold/matrix components - Can precisely deposit multiple cell types and ECM components during fabrication | - Current models are still relatively simple compared to in vivo - Fabrication of bioprinted constructs can be technically challenging and remains relatively costly | [169,198,199] |
6.3.1. Hydrogels Models for Tumorigenic Vascular Development
6.3.2. Microfluidics to Model Vascularised Tumour Environments
6.3.3. 3D Bioprinting to Model Vascularised Tumour Environments
7. Conclusions and Future Perspectives
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ECM | Extracellular matrix |
3D | Three-dimensional |
miRNA | Micro-RNA |
mRNA | Messenger-RNA |
EMT | Epithelial-to-mesenchymal transition |
CSC | Cancer stem cells |
GAG | Glycosaminoglycan |
MMP | Matrix metalloproteinase |
MAPL | Mitogen-activated protein kinase |
PI3K | Phosphoinositide 3-kinase |
Crumbs3 | Crumbs cell polarity complex component 3 |
Patj | Pals1-associated tight junction protein |
Par3 | Partitioning defective 3 |
Par6 | Partitioning defective 6 |
aPKC | Atypical protein kinase |
E-cadherin | Epithelial cadherin |
Cdc42 | Cell division cycle 42 |
Lgl | Lethal 2 giant larvae |
Dlg | Discs large |
JAM | Junction adhesion molecules |
PTEN | Phosphatase and tensin homolog |
MDCK | Madin–Darby canine kidney |
2D | Two-dimensional |
RGD | Arg-Gly-Asp |
SAPH | Self-assembling peptide hydrogel |
YGSIR | Tyr–Ile–Gly–Ser–Arg |
VEGFA | Vascular endothelial growth factor A |
oncomiRs | Cancer-related miRNAs |
PDCD4 | Programmed cell death protein 4 |
TIMP3 | Tissue inhibitor of metalloproteinase 3 |
RECK | Reversion-inducing cysteine-rich protein with Kazal motifs |
PEG | Polyethylene glycol |
MMP-2 | Metalloproteinase-2 |
MMP-9 | Metalloproteinase-9 |
Col1A1 | Collagen type I alpha 1 |
SqCa | Squamous cell carcinoma |
AdCa | Adenocarcinoma |
HPV | Human papillomavirus |
EV | Extracellular vesicle |
GelMA | Gelatin methacryloyl |
TGF-β | Transforming growth factor-beta |
CAF | Cancer-associated fibroblast |
HIF-1α | Hypoxia-inducible factor 1-alpha |
EC | Endothelial cell |
EPC | Endothelial progenitor cell |
VEGFR2 | Vascular endothelial growth factor receptor 2 |
SDF-1 | Stromal cell-derived factor 1 |
FGF | Fibroblast growth factor |
VSMC | Vascular smooth muscle cell |
HUVEC | Human umbilical vein endothelial cell |
Ang-1 | Angiopoietin-1 |
CLIC3 | Chloride intracellular channel protein 3 |
ECFC-EC | Endothelial colony forming cell-derived EC |
GSC | Glioma stem cell |
ADSC | Adipose-derived stromal cells |
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Cancer Type | Expression Profile | Diagnostic Value | Prognostic Value | Diagnostic and Prognostic Value |
---|---|---|---|---|
Breast | Downregulated | let-7b-5p, let-7c-5p | miR-409-3p | |
Upregulated | miR-195, miR-376c, miR-409-3p, miR-148b, miR-299-5p, miR-145, miR-191, miR-382, miR-215, miR-133a, miR-133b, miR-92a, miR-192, miR-1, miR-411, miR-195, miR-202 | miR-122 miR-141 | miR-21, miR-34a, miR-210, miR-10b, miR-375, miR-125b, miR-801, miR-155 | |
Pancreatic | Downregulated | miR-100-5p, miR-375 | miR-718 | |
Upregulated | miR-378 *, miR-409-3p, miR-1290, miR-26a, miR-18a | miR-146b-3p, miR-200a, miR-200c, miR-210, miR-221, miR-21, miR-194 | miR-141, miR-375 | |
Prostate | Downregulated | miR-16, miR-199a, miR-21 | ||
Upregulated | miR-378 *, miR-409-3p, miR-1290, miR-26a, miR-18a | miR-146b-3p, miR-210, miR-21, miR-221, miR-19, miR-200a, miR-200c | miR-141, miR-375 | |
Non-small-cell lung carcinoma | Downregulated | let-7b-5p, let-7c-5p | ||
Upregulated | miR-20a-5p, miR-141-3p, miR-145-5p, miR-155-5p, miR-223-3p | miR-320b, miR-23b-3p, miR-10b-3p, miR-195-5p | miR-21-5p |
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Larrea Murillo, L.; Green, M.; Mahon, N.; Saiani, A.; Tsigkou, O. Modelling Cancer Pathophysiology: Mechanisms and Changes in the Extracellular Matrix During Cancer Initiation and Early Tumour Growth. Cancers 2025, 17, 1675. https://doi.org/10.3390/cancers17101675
Larrea Murillo L, Green M, Mahon N, Saiani A, Tsigkou O. Modelling Cancer Pathophysiology: Mechanisms and Changes in the Extracellular Matrix During Cancer Initiation and Early Tumour Growth. Cancers. 2025; 17(10):1675. https://doi.org/10.3390/cancers17101675
Chicago/Turabian StyleLarrea Murillo, Luis, Megan Green, Niall Mahon, Alberto Saiani, and Olga Tsigkou. 2025. "Modelling Cancer Pathophysiology: Mechanisms and Changes in the Extracellular Matrix During Cancer Initiation and Early Tumour Growth" Cancers 17, no. 10: 1675. https://doi.org/10.3390/cancers17101675
APA StyleLarrea Murillo, L., Green, M., Mahon, N., Saiani, A., & Tsigkou, O. (2025). Modelling Cancer Pathophysiology: Mechanisms and Changes in the Extracellular Matrix During Cancer Initiation and Early Tumour Growth. Cancers, 17(10), 1675. https://doi.org/10.3390/cancers17101675