Melanoma Cells Produce Large Vesicular-Bodies That Cause Rapid Disruption of Brain Endothelial Barrier-Integrity and Disassembly of Junctional Proteins
Abstract
:1. Introduction
1.1. Melanoma Brain Metastasis
1.2. Extracellular Vesicles in Cancer Progression and Metastasis
1.3. New Zealand Melanoma and Their Vesicular-Bodies
2. Results
2.1. Initial Detection of the NZM Suspension Subpopulation Shows Clear Evidence of Enzymatic Activity
2.2. NZM Suspension Subpopulation Substantially and Rapidly Decreases Brain Endothelial Barrier Resistance
2.3. Imaging Data Show NZM7-S Population Adheres to and Disrupts Brain Endothelial Barrier
2.4. Live-Cell Imaging Shows NZM7-S Material Disrupting the Brain Endothelial Cells in a Transcellular Manner
2.5. Confocal Microscopy Reveals Intricate Details about NZM7-S Interaction with the Brain Endothelial Cells
2.6. ECIS Measurements Show That CTR++ NZM7-S Material Decrease the Brain Endothelial Barrier Resistance
3. Discussion
4. Materials and Methods
4.1. Culture of Human Cerebral Microvascular Endothelial Cells (hCMVECs)
4.2. Culture of New Zealand Melanoma (NZM) Cells
4.3. Cell Harvest and Passaging
4.4. Collection of NZM7 Suspension Material
4.5. Bright Field Imaging of Cells
4.6. Flow Cytometry
4.7. Conventional Analysis and Gating
4.8. Electric Cell-Substrate Impedance Sensing (ECIS)
4.9. ECIS Set up
4.10. ECIS Modelling
4.11. Addition of Melanoma Cells to hCMVECs
4.12. Addition of Suspension Material to hCMVECs
4.13. Labelling of the NZM7 Cultures for Imaging
4.14. Immunocytochemistry
4.15. Live Cell Imaging
4.16. Operetta CLS Imaging System
4.17. Confocal Imaging and Image Analysis
4.18. FACS Sorting of NZM7-S
4.19. Statistical Analysis
5. Future Perspectives
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Spurling, D.; Anchan, A.; Hucklesby, J.; Finlay, G.; Angel, C.E.; Graham, E.S. Melanoma Cells Produce Large Vesicular-Bodies That Cause Rapid Disruption of Brain Endothelial Barrier-Integrity and Disassembly of Junctional Proteins. Int. J. Mol. Sci. 2023, 24, 6082. https://doi.org/10.3390/ijms24076082
Spurling D, Anchan A, Hucklesby J, Finlay G, Angel CE, Graham ES. Melanoma Cells Produce Large Vesicular-Bodies That Cause Rapid Disruption of Brain Endothelial Barrier-Integrity and Disassembly of Junctional Proteins. International Journal of Molecular Sciences. 2023; 24(7):6082. https://doi.org/10.3390/ijms24076082
Chicago/Turabian StyleSpurling, Dayna, Akshata Anchan, James Hucklesby, Graeme Finlay, Catherine E. Angel, and E. Scott Graham. 2023. "Melanoma Cells Produce Large Vesicular-Bodies That Cause Rapid Disruption of Brain Endothelial Barrier-Integrity and Disassembly of Junctional Proteins" International Journal of Molecular Sciences 24, no. 7: 6082. https://doi.org/10.3390/ijms24076082