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
| Autor: | Anita K. Luu, Mia Cadieux, Mackenzie Wong, Rachel Macdonald, Robert Jones, Dongsic Choi, Michelle Oblak, Brigitte Brisson, Scott Sauer, James Chafitz, David Warshawsky, Geoffrey A. Wood, Alicia M. Viloria-Petit |
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| Rok vydání: | 2021 |
| Předmět: |
Proteomics
Osteosarcoma Proteasome Endopeptidase Complex Organic Chemistry Bone Neoplasms General Medicine Catalysis Computer Science Applications Inorganic Chemistry Extracellular Vesicles Dogs Cell Line Tumor Trans-Activators Animals Humans Physical and Theoretical Chemistry osteosarcoma extracellular vesicles tissue explants biomarker discovery molecular targets Molecular Biology Spectroscopy Cell Proliferation |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 6; Pages: 3256 |
| ISSN: | 1422-0067 |
| Popis: | Osteosarcoma (OS) is a highly malignant bone tumour that has seen little improvement in treatment modalities in the past 30 years. Understanding what molecules contribute to OS biology could aid in the discovery of novel therapies. Extracellular vesicles (EVs) serve as a mode of cell-to-cell communication and have the potential to uncover novel protein signatures. In our research, we developed a novel pipeline to isolate, characterize, and profile EVs from normal bone and osteosarcoma tissue explants from canine OS patients. Proteomic analysis of vesicle preparations revealed a protein signature related to protein metabolism. One molecule of interest, PSMD14/Rpn11, was explored further given its prognostic potential in human and canine OS, and its targetability with the drug capzimin. In vitro experiments demonstrated that capzimin induces apoptosis and reduces clonogenic survival, proliferation, and migration in two metastatic canine OS cell lines. Capzimin also reduces the viability of metastatic human OS cells cultured under 3D conditions that mimic the growth of OS cells at secondary sites. This unique pipeline can improve our understanding of OS biology and identify new prognostic markers and molecular targets for both canine and human OS patients. |
| Databáze: | OpenAIRE |
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