Modeling the Role of Cancer-Associated Fibroblasts in Tumor Cell Invasion
Abstract
:Simple Summary
Abstract
1. Introduction
2. Early Modeling of Cell Migration and Invasion
3. CAFs and the Tumor Microenvironment
4. Incorporation of CAFs into Pre-Existing Models
4.1. Scratch Wound/Exclusion Zone Invasion Assay
4.2. Transwell Invasion Assay
4.3. Spheroid Invasion Assay
5. The Rise of Novel In Vitro Models
5.1. Matrix Modifications
5.2. Novel Alternative Invasion Assays
5.3. Using Organoids in Invasion Assays
6. Compartmentalizing the Tumor
7. Engineering a Dynamic Tumor
7.1. Making It Small
7.2. Expanding the Utility of Small Devices
7.3. Observing Matrix Changes
8. Conclusions and Current Perspectives
Author Contributions
Funding
Conflicts of Interest
References
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Assay | Ref. | Type | Technical Complexity | Material Availability 1 | HT Potential 2 | Compatible Imaging Techniques 3,4 | Quantitative Measurement(s) 4 | Location of CAFs in Assay 4 | Cell Collection from Assay |
---|---|---|---|---|---|---|---|---|---|
Scratch Wound | [15,16] | Timecourse | Low | Common + Commercial | Yes | Live Cell (PC, Fluorescence) | Speed of gap closure | Mixed with tumor cells | Yes |
Exclusion Zone | [17,18,19] | Timecourse | Low | Commercial | Yes | Live Cell (PC, Fluorescence) | Speed of gap closure | Mixed with tumor cells | Yes |
Transwell | [13,21] | Endpoint | Low | Commercial | No | Crystal Violet Staining | # of cells on membrane | See Figure 1C | No |
Vertical Gel | [53] | Endpoint | Moderate | Somewhat Specialized | No | H&E Staining of sections | Invasive Index 5 | In matrix separated from tumor cells | No |
Spheroid | [29] | Timecourse | Low | Common | Yes | Live cell (PC, Fluorescence) | Invasive Area, Circularity | Mixed with tumor cells; Can be in surrounding matrix | Yes |
Matrigel Drop | [67] | Both | Low | Common | No | Live cell (PC, Fluorescence), IF staining | Invasive Area (Migrating edge) | Can be in surrounding matrix | No |
3D Dumbbell | [68] | Timecourse | Moderate | Common | No | Live cell (PC, Fluorescence) | N/A | In matrix separated from tumor cells | No |
Organoids | [76,77] | Both | Moderate | Somewhat Specialized | Yes | Live cell (PC, Fluorescence), IF staining, H&E staining of sections | Organoid features (Number, size, circularity) | In surrounding matrix | Yes |
Tumoroid | [78,79] | Endpoint | Moderate | Commercial | No | IF staining, Optical Projection Tomography | Invasion features (Distance, Area, Aggregate size) | In stromal compartment | Yes |
TRACER | [81] | Endpoint | High | Specialized | No | IF staining, Scanning Electron Microscopy | Proportion of tumor cells in layer of interest | In matrix separated or mixed with tumor cells | Yes |
GLAnCE | [84] | Timecourse | Moderate | Specialized | No | Live Cell (Fluorescence) | Interface features (# of strand structures, Aggregate circularity) | In matrix separated or mixed with tumor cells | Yes |
LumeNEXT Chip | [87] | Timecourse | High | Specialized | No | Live cell (Fluorescence), Second Harmonic Generation | Cell migration distance, # of migration cells | In surrounding matrix | No |
Iuvo Invasion Slide | [89] | Timecourse | High | Commercial | No | Live Cell (Fluorescence) | # of invading cells | Added to same or opposite port from tumor cells (See Figure 2C(i)) | No |
Microfluidics Chip | [91] | Both | High | Specialized | No | Live cell (PC, Fluorescence), IF staining | Invasive cell features (Distance, Number, Speed) | In matrix separated from tumor cells | Yes |
Mini-Pillar | [93,94,95] | Both | High | Specialized | Yes | Live cell (Fluorescence), IF staining of whole sample or sections | Length and # of protrusions, Circularity and # of spheroids | In matrix separated from tumor cells | Yes |
HT-HC Platform | [97] | Endpoint | High | Specialized | Yes | IF staining | Invasive cell features (Distance, Number) | Mixed with tumor cells | No |
Open-top Model | [99] | Both | Moderate | Specialized | No | Live cell (PC, Fluorescence), Real time cell tracking, IF staining, Confocal reflectance microscopy | Area disorder 5, Migration Index 5, Speed of Migration | In surrounding matrix | Yes |
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Poon, S.; Ailles, L.E. Modeling the Role of Cancer-Associated Fibroblasts in Tumor Cell Invasion. Cancers 2022, 14, 962. https://doi.org/10.3390/cancers14040962
Poon S, Ailles LE. Modeling the Role of Cancer-Associated Fibroblasts in Tumor Cell Invasion. Cancers. 2022; 14(4):962. https://doi.org/10.3390/cancers14040962
Chicago/Turabian StylePoon, Stephanie, and Laurie E. Ailles. 2022. "Modeling the Role of Cancer-Associated Fibroblasts in Tumor Cell Invasion" Cancers 14, no. 4: 962. https://doi.org/10.3390/cancers14040962