Knockout of MMP3 Weakens Solid Tumor Organoids and Cancer Extracellular Vesicles
Abstract
:1. Introduction
2. Results
2.1. MMP3 Knockout Reduces the Release of CD9 and CD63 within Extracellular Vesicles
2.2. MMP3 Knockout Impacts Physical Integrities of Extracellular Vesicles
2.3. Loss of the Mmp3 Gene Reduces the In Vitro Tumorigenicity
2.4. The Addition of MMP3-Rich EVs Accelerated the In Vitro Tumorigenesis of MMP3-KO Cells
2.5. Establishment of Fluorescent-Labeled LuM1 and MMP3-Null Cells
2.6. Penetration of MMP3-Rich EVs into Organoids
2.7. The Knockout of the Mmp3 Gene Significantly Decreased the Transmissive Potential of Tumoroid-Derived EVs
2.8. MMP3-Rich EVs and CM Rescue the Cell Proliferation of MMP3-KO Tumoroids
3. Discussion
3.1. Summary
3.2. Potential Mechanism of How MMP3 Promotes Tumorigenesis
3.3. Potential Role of MMP3 in Cytoprotection
3.4. Release of L-EVs and s-EVs from 3D Tumoroids
3.5. Fluorescent Labeling of EVs
3.6. Inter MMPs Regulation
4. Materials and Methods
4.1. Cells
4.2. Tumoroid Culture
4.3. Re-Seeding Assay
4.4. Preparation of EVs and Conditioned Media
4.5. Transmission Electron Microscopy
4.6. Particle Diameter Distribution
4.7. Western Blotting
4.8. Coomassie Brilliant Blue Staining
4.9. EV-Driven In Vitro Tumorigenesis
4.10. Palm Fluorescent Cells
4.11. EVs Exchange Assay
4.12. Confocal Laser-Scanning Microscopy
4.13. Immunofluorescence of Tumoroids
4.14. Hematoxylin and Eosin Staining
4.15. Tracing EV-Uptake In Vitro
4.16. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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LuM1-EV | MMP3-KO-EV | ||||||
---|---|---|---|---|---|---|---|
Peak | Diameter (nm) | Intensity (%) | Width (nm) | Peak | Diameter (nm) | Intensity (%) | Width (nm) |
1 | 561.4 | 48.6 | 164.9 | 1 | 464.9 | 76.6 | 155.3 |
2 | 119.3 | 38.3 | 31.8 | 2 | 83.9 | 20.2 | 20.4 |
3 | 8.0 | 6.8 | 1.53 | 3 | 5,374 | 3.2 | 326.1 |
LuM1 | MMP3-KO | |
---|---|---|
Total tumoroid area (μm2) | 331,701 | 64,148 |
Number of necrotic areas | 1 | 5 |
Sum of necrotic areas (μm2) | 4807 | 9351 |
Necrosis % | 1 | 15 |
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Taha, E.A.; Sogawa, C.; Okusha, Y.; Kawai, H.; Oo, M.W.; Elseoudi, A.; Lu, Y.; Nagatsuka, H.; Kubota, S.; Satoh, A.; et al. Knockout of MMP3 Weakens Solid Tumor Organoids and Cancer Extracellular Vesicles. Cancers 2020, 12, 1260. https://doi.org/10.3390/cancers12051260
Taha EA, Sogawa C, Okusha Y, Kawai H, Oo MW, Elseoudi A, Lu Y, Nagatsuka H, Kubota S, Satoh A, et al. Knockout of MMP3 Weakens Solid Tumor Organoids and Cancer Extracellular Vesicles. Cancers. 2020; 12(5):1260. https://doi.org/10.3390/cancers12051260
Chicago/Turabian StyleTaha, Eman A., Chiharu Sogawa, Yuka Okusha, Hotaka Kawai, May Wathone Oo, Abdellatif Elseoudi, Yanyin Lu, Hitoshi Nagatsuka, Satoshi Kubota, Ayano Satoh, and et al. 2020. "Knockout of MMP3 Weakens Solid Tumor Organoids and Cancer Extracellular Vesicles" Cancers 12, no. 5: 1260. https://doi.org/10.3390/cancers12051260
APA StyleTaha, E. A., Sogawa, C., Okusha, Y., Kawai, H., Oo, M. W., Elseoudi, A., Lu, Y., Nagatsuka, H., Kubota, S., Satoh, A., Okamoto, K., & Eguchi, T. (2020). Knockout of MMP3 Weakens Solid Tumor Organoids and Cancer Extracellular Vesicles. Cancers, 12(5), 1260. https://doi.org/10.3390/cancers12051260