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Updated: Sep 29, 2025
A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells
Published on: May 6, 2018
Proteomic Assessment of Extracellular Vesicles from Canine Tissue Explants as a Pipeline to Identify Molecular
Anita K Luu1, Mia Cadieux1, Mackenzie Wong1
1Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.
Abstract:
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.
Insights
Researchers identified a novel protein signature in extracellular vesicles from canine osteosarcoma (OS). Targeting PSMD14/Rpn11 with capzimin showed promise in reducing OS cell growth and metastasis in preclinical models.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteosarcoma (OS) is a highly malignant bone cancer with limited treatment advancements.
- Extracellular vesicles (EVs) are crucial for cell-to-cell communication and can reveal novel protein signatures.
- Understanding OS molecular mechanisms is key to developing new therapeutic strategies.
Purpose of the Study:
- To develop a pipeline for isolating, characterizing, and profiling EVs from canine OS tissues.
- To identify novel protein signatures and potential therapeutic targets in OS.
- To evaluate the efficacy of targeting PSMD14/Rpn11 with capzimin in OS models.
Main Methods:
- Developed a novel pipeline for EV isolation and characterization from canine OS explants.
- Performed proteomic analysis to identify EV protein signatures.
- Conducted in vitro experiments using canine and human OS cell lines to assess capzimin's effects.
Main Results:
- Identified an EV protein signature related to protein metabolism.
- PSMD14/Rpn11 was identified as a potential prognostic marker and therapeutic target.
- Capzimin treatment induced apoptosis and reduced clonogenic survival, proliferation, and migration in canine OS cells.
- Capzimin reduced the viability of human OS cells in 3D culture.
Conclusions:
- The developed pipeline aids in understanding OS biology and identifying new prognostic markers.
- PSMD14/Rpn11 is a promising therapeutic target for both canine and human osteosarcoma.
- Capzimin demonstrates potential as a novel therapeutic agent for osteosarcoma treatment.
