Proteomic Assessment of Extracellular Vesicles from Canine Tissue Explants as a Pipeline to Identify Molecular Targets in Osteosarcoma: PSMD14/Rpn11 as a Proof of Principle
Abstract
:1. Introduction
2. Results
2.1. Extracellular Vesicles Can Be Successfully Isolated from OS and Normal Bone Tissue Explants
2.2. Twenty-Nine Proteins Are Significantly Increased in OS-Derived Vesicles Compared to Normal Bone-Derived Vesicles
2.3. Proteasome Components Are Clinically Relevant and of Current Interest in the Field of OS
2.4. OS Cell Lines Are Sensitive to Capzimin Treatment and Demonstrate Increased Ubiquitinated Products following Treatment
2.5. Capzimin Induces Apoptosis in a Dose-Dependent Manner in Canine OS Cells
2.6. Capzimin Reduces Clonogenic Survival, Cell Growth, and Migration
2.7. Capzimin Reduces Viability Compared to Doxorubicin Alone at Low Doses
2.8. Capzimin Reduces Viability of Metastatic Human OS Cells in 3D Conditions Resembling Secondary Sites
3. Discussion
4. Materials and Methods
4.1. Sample Acquisition and Explant Culture
4.2. Vesicle Isolation
4.3. Vesicle Lysis
4.4. Dynamic Light Scattering
4.5. Transmission Electron Micrscopy
4.6. Vesicle Protein Quantification
4.7. Ultra High Performance Liquid Chromatography and Tandem Mass Spectrometry (UHPLC-MS/MS)
4.8. Associations of mRNA Expression of Identified Proteins with Clinical Outcome
4.9. OS Cell Culture Conditions
4.10. Capzimin IC50 Dose Response
4.11. Capzimin Treatment & Lysate Collection for the Detection of Apoptosis
4.12. Cell Lysate Protein Quantification
4.13. Immunoblotting of Vesicle Fractions and Capzimin Treated Cells
4.14. Ubiqutinated Protein Enrichment
4.15. Annexin-V FITC and Propidium Iodide (PI) Staining and Flow Cytometry
4.16. Clonogenic Survival Assay
4.17. Phosphorylated Histone-H3 (pHH3) Immunoblabelling and Quantification
4.18. Cell Cycle Analysis
4.19. Transwell Assay
4.20. Combination Treatment: Capzimin and Doxorubicin
4.21. Assessment of MG63.3 Cytotoxicity in 2D and 3D Culture
4.22. Statistical Analyses
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Luu, A.K.; Cadieux, M.; Wong, M.; Macdonald, R.; Jones, R.; Choi, D.; Oblak, M.; Brisson, B.; Sauer, S.; Chafitz, J.; et al. Proteomic Assessment of Extracellular Vesicles from Canine Tissue Explants as a Pipeline to Identify Molecular Targets in Osteosarcoma: PSMD14/Rpn11 as a Proof of Principle. Int. J. Mol. Sci. 2022, 23, 3256. https://doi.org/10.3390/ijms23063256
Luu AK, Cadieux M, Wong M, Macdonald R, Jones R, Choi D, Oblak M, Brisson B, Sauer S, Chafitz J, et al. Proteomic Assessment of Extracellular Vesicles from Canine Tissue Explants as a Pipeline to Identify Molecular Targets in Osteosarcoma: PSMD14/Rpn11 as a Proof of Principle. International Journal of Molecular Sciences. 2022; 23(6):3256. https://doi.org/10.3390/ijms23063256
Chicago/Turabian StyleLuu, Anita K., Mia Cadieux, Mackenzie Wong, Rachel Macdonald, Robert Jones, Dongsic Choi, Michelle Oblak, Brigitte Brisson, Scott Sauer, James Chafitz, and et al. 2022. "Proteomic Assessment of Extracellular Vesicles from Canine Tissue Explants as a Pipeline to Identify Molecular Targets in Osteosarcoma: PSMD14/Rpn11 as a Proof of Principle" International Journal of Molecular Sciences 23, no. 6: 3256. https://doi.org/10.3390/ijms23063256