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

Espejo, C, Wilson, R ORCID: 0000-0003-0152-4394, Willms, E, Ruiz-Aravena, M, Pye, RJ ORCID: 0000-0002-1001-3329, Jones, M ORCID: 0000-0001-7558-9022, Hill, AF, Woods, GM ORCID: 0000-0001-8421-7917 and Lyons, AB ORCID: 0000-0002-8508-5853 2021 , 'Extracellular vesicle proteomes of two transmissible cancers of Tasmanian devils reveal tenascin-C as a serum-based differential diagnostic biomarker' , Cellular and Molecular Life Sciences, vol. 78, no. 23 , pp. 7537-7555 , doi: 10.1007/s00018-021-03955-y.

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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.

Item Type: Article
Authors/Creators:Espejo, C and Wilson, R and Willms, E and Ruiz-Aravena, M and Pye, RJ and Jones, M and Hill, AF and Woods, GM and Lyons, AB
Keywords: extracellular vesicles, exosomes, microvesicles, marsupials, size exclusion chromatography, proteomics, cancer diagnostics
Journal or Publication Title: Cellular and Molecular Life Sciences
Publisher: Birkhauser Verlag Ag
ISSN: 1420-682X
DOI / ID Number: 10.1007/s00018-021-03955-y
Copyright Information:

© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2021

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