Cathelicidin-3 associated with serum extracellular vesicles enables early diagnosis of a transmissible cancer

Espejo, Camila; Wilson, Richard; Pye, Ruth J.; Ratcliffe, Julian; Ruiz‐Aravena, Manuel; Willms, Eduard; Wolfe, Barrett W.; Hamede, Rodrigo; Hill, Andrew F.; Jones, Menna Lloyd; Woods, Gregory M.; Lyons, A. Bruce

doi:10.1101/2021.12.06.471373

Cited by 1 publication

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References 63 publications

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“…Since the emergence of a coordinated response to the DFT1 epidemic, developing a test for the early detection of DFTD has been a high priority for conservation management [50]. Using contemporary methodology for the isolation of EVs and quantitative proteomics, we demonstrated the means to develop an early DFT1 diagnostic [51]. Our study found that the protein cathelicidin-3 (CATH3) was enriched in serum EVs of both devils with clinical DFT1 infection and latent devils 3-6 months before diagnosis.…”

Section: Extracellular Vesiclesmentioning

confidence: 99%

Challenges of an Emerging Disease: The Evolving Approach to Diagnosing Devil Facial Tumour Disease

et al. 2021

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Devil Facial Tumour Disease (DFTD) is an emerging infectious disease that provides an excellent example of how diagnostic techniques improve as disease-specific knowledge is generated. DFTD manifests as tumour masses on the faces of Tasmanian devils, first noticed in 1996. As DFTD became more prevalent among devils, karyotyping of the lesions and their devil hosts demonstrated that DFTD was a transmissible cancer. The subsequent routine diagnosis relied on microscopy and histology to characterise the facial lesions as cancer cells. Combined with immunohistochemistry, these techniques characterised the devil facial tumours as sarcomas of neuroectodermal origin. More sophisticated molecular methods identified the origin of DFTD as a Schwann cell, leading to the Schwann cell-specific protein periaxin to discriminate DFTD from other facial lesions. After the discovery of a second facial cancer (DFT2), cytogenetics and the absence of periaxin expression confirmed the independence of the new cancer from DFT1 (the original DFTD). Molecular studies of the two DFTDs led to the development of a PCR assay to differentially diagnose the cancers. Proteomics and transcriptomic studies identified different cell phenotypes among the two DFTD cell lines. Phenotypic differences were also reflected in proteomics studies of extracellular vesicles (EVs), which yielded an early diagnostic marker that could detect DFTD in its latent stage from serum samples. A mesenchymal marker was also identified that could serve as a serum-based differential diagnostic. The emergence of two transmissible cancers in one species has provided an ideal opportunity to better understand transmissible cancers, demonstrating how fundamental research can be translated into applicable and routine diagnostic techniques.

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Section: Extracellular Vesiclesmentioning

confidence: 99%