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Extracellular vesicle proteomes of two transmissible cancers of Tasmanian devils reveal tenascin-C as a serum-based differential diagnostic biomarker

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Abstract

The iconic Tasmanian devil (Sarcophilus harrisii) is endangered due to the transmissible cancer Devil Facial Tumour Disease (DFTD), of which there are two genetically independent subtypes (DFT1 and DFT2). While DFT1 and DFT2 can be differentially diagnosed using tumour biopsies, there is an urgent need to develop less-invasive biomarkers that can detect DFTD and distinguish between subtypes. Extracellular vesicles (EVs), the nano-sized membrane-enclosed vesicles present in most biofluids, represent a valuable resource for biomarker discovery. Here, we characterized the proteome of EVs from cultured DFTD cells using data-independent acquisition–mass spectrometry and an in-house spectral library of > 1500 proteins. EVs from both DFT1 and DFT2 cell lines expressed higher levels of proteins associated with focal adhesion functions. Furthermore, hallmark proteins of epithelial–mesenchymal transition were enriched in DFT2 EVs relative to DFT1 EVs. These findings were validated in EVs derived from serum samples, revealing that the mesenchymal marker tenascin-C was also enriched in EVs derived from the serum of devils infected with DFT2 relative to those infected with DFT1 and healthy controls. This first EV-based investigation of DFTD increases our understanding of the cancers’ EVs and their possible involvement in DFTD progression, such as metastasis. Finally, we demonstrated the potential of EVs to differentiate between DFT1 and DFT2, highlighting their potential use as less-invasive liquid biopsies for the Tasmanian devil.

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Data availability

The mass spectrometry raw proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [74] partner repository with the dataset identifier PXD020766 (cell lysate and EV samples); and PXD025579 (serum EV samples).

Code availability

Not applicable.

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Acknowledgements

We would like to acknowledge all the members of the devil and wild immunology group for their advice and guidance. We would also like to thank Ginny Ralph for providing care of captive devils, the Bonorong Wildlife Sanctuary for providing access to Tasmanian devils and Dr Alexandre Kreiss for collecting the blood and to the Save the Tasmanian Devil Program for provision of samples. The authors would also like to acknowledge La Trobe University Bioimaging Platform for their support with TEM analysis.

Funding

This work was supported by the National Geographic explorer early career grant, Holsworth Wildlife Research Endowment grants, the University of Tasmania Foundation through funds raised by the Save the Tasmanian Devil Appeal. Proteomics infrastructure was funded by ARC LE180100059. Sample collection from wild devils was funded by US National Institutes of Health (NIH) grant R01-GM126563-01 and US National Science Foundation (NSF) grant DEB1316549 as part of the joint NIH-NSF-USDA Ecology and Evolution of Infectious Diseases program.

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Authors and Affiliations

  1. Tasmanian School of Medicine, College of Health and Medicine, University of Tasmania, Hobart, TAS, 7000, Australia

    Camila Espejo & A. Bruce Lyons

  2. Central Science Laboratory, University of Tasmania, Hobart, TAS, 7005, Australia

    Richard Wilson

  3. Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, 3083, Australia

    Eduard Willms & Andrew F. Hill

  4. Department of Microbiology and Immunology, Montana State University, Bozeman, MT, 59717, USA

    Manuel Ruiz-Aravena

  5. Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, TAS, 7000, Australia

    Ruth J. Pye & Gregory M. Woods

  6. School of Natural Sciences, University of Tasmania, Hobart, TAS, 7001, Australia

    Manuel Ruiz-Aravena & Menna E. Jones

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  1. Camila Espejo
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Correspondence to Camila Espejo.

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All animal procedures were performed under a Standard Operating Procedure approved by the General Manager, Natural and Cultural Heritage Division, Tasmanian Government Department of Primary Industries, Parks, Water and the Environment and under the auspices of the University of Tasmania Animal Ethics Committee (permit numbers: A0017550, A0013326, A0015835).

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Espejo, C., Wilson, R., Willms, E. et al. Extracellular vesicle proteomes of two transmissible cancers of Tasmanian devils reveal tenascin-C as a serum-based differential diagnostic biomarker. Cell. Mol. Life Sci. 78, 7537–7555 (2021). https://doi.org/10.1007/s00018-021-03955-y

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