Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 6, Pages -Publisher
MDPI
DOI: 10.3390/ijms23063256
Keywords
osteosarcoma; extracellular vesicles; tissue explants; biomarker discovery; molecular targets
Funding
- OVC Pet Trust [053666]
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Osteosarcoma (OS) is a highly malignant bone tumor with limited improvements in treatment. Understanding the molecules contributing to OS biology can lead to the discovery of novel therapies. This study demonstrates the potential of extracellular vesicles (EVs) in revealing protein signatures related to OS and highlights a specific protein, PSMD14/Rpn11, as a potential prognostic marker and therapeutic target for OS.
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.
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