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Uncovering the pathways related with extracellular vesicles derived from Devil Facial Tumour cells (DFTD).

ABSTRACT: Tasmanian devils are threatened with extinction because of two genetically independent transmissible cancers which are termed as Devil Facial Tumour Disease one and two (DFTD-1 and DFTD-2). The cancers are indistinguishable by gross examination and require laboratory procedures such as immunohistochemistry and/or PCR for diagnosis. Here we used proteomics to analyse extracellular vesicles from DFTD cells to better understand the potentail role of EV's in DFTD cancer metastasis.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Sarcophilus Harrisii

TISSUE(S): Cell Culture

SUBMITTER: Richard Wilson

LAB HEAD: Dr Richard Wilson

PROVIDER: PXD020766 | Pride | 2023-04-27

REPOSITORIES: Pride

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			Action	DRS
	20020312_CE_Lys_F1.raw	Raw
	20020312_CE_Lys_F10.raw	Raw
	20020312_CE_Lys_F11.raw	Raw
	20020312_CE_Lys_F12.raw	Raw
	20020312_CE_Lys_F13.raw	Raw

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Publications

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

Espejo Camila C Wilson Richard R Willms Eduard E Ruiz-Aravena Manuel M Pye Ruth J RJ Jones Menna E ME Hill Andrew F AF Woods Gregory M GM Lyons A Bruce AB

Cellular and molecular life sciences : CMLS 20211016 23

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, repres ...[more]

PMID: 34655299

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The Tasmanian devil transcriptome reveals Schwann cell origins of a clonally transmissible cancer (small RNA sequencing)

Project description:The Tasmanian devil, a marsupial carnivore, is endangered due to the emergence of a clonally transmissible cancer known as Devil Facial Tumor Disease (DFTD). This fatal cancer is clonally derived and is an allograft transmitted between devils by biting. We performed a large-scale genetic analysis of DFTD with microsatellite genotyping, mitochondrial genome analysis, as well as deep sequencing of the DFTD transcriptome and miRNAs. These studies confirm that DFTD is a monophyletic clonally transmissible tumor, and suggest that the disease is of Schwann cell origin. On the basis of these results we have generated a diagnostic marker for DFTD, and identify a suite of genes of relevance to DFTD pathology and transmission. We provide a genomic dataset for the Tasmanian devil, which is applicable to cancer diagnosis, disease evolution and conservation biology. This submission contains only small RNA sequence data from this study. Small RNA (18 - 24 nt) sequences from 15 Tasmanian devil (Sarcophilus harrisii) tissue samples

2010-01-01 | E-GEOD-18352 | biostudies-arrayexpress

The Tasmanian devil transcriptome reveals Schwann cell origins of a clonally transmissible cancer (small RNA sequencing)

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The ERBB-STAT3 Axis Drives Tasmanian Devil Facial Tumor Disease

Project description:The marsupial Tasmanian devil (Sarcophilus harrisii) faces extinction due to transmissible devil facial tumor disease (DFTD). To unveil the culprit molecular underpinnings, we designed an approach that combines sensitivity to drugs with an integrated systems-biology characterization. Sensitivity to inhibitors of the ERBB family of receptor tyrosine kinases correlated with their overexpression, suggesting a causative link. Proteomic and DNA methylation analyses revealed tumor-specific signatures linked to oncogenic signaling hubs including evolutionary conserved STAT3. Indeed, inhibition of ERBB blocked phosphorylation of STAT3 and arrested cancer cells. Blockade of ERBB signaling prevented tumor growth in a xenograft model and resulted in recovery of MHC-I gene expression. This link between the hyperactive ERBB-STAT3 axis and decreased MHC-I mediated tumor immunosurveillance provides mechanistic insights into horizontal transmissibility and lets us propose a dual chemo-immunotherapeutic strategy to save Tasmanian devils from DFTD.

2019-01-18 | PXD009283 | Pride

Tasmanian devil facial tumour-derived extracellular vesicles reveal mesenchymal transition markers and adhesion molecules related to metastasis.

Project description: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 >1,500 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 clinical 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 that highlights their potential use as less invasive liquid biopsies for the Tasmanian devil and other animals.

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Biomarker discovery for Tasmanian Devil Facial Tumour Disease using serum-derived extracellular vesicles

Project description:Serum extracellular vesicles were obtained from Tasmanian devils with confirmed DFTD, heathy devils from captive and wild populations and from latent devils with no evidence of facial tumours.

2022-03-14 | PXD021480 | Pride

Tasmanian Devil Facial Tumour Disease - Imiquimod treatment of DFT1 cells

Project description:A Tasmanian Devil Facial Tumour Disease (DFTD) tumor cell line was treated with the drug Imiquimod

2018-04-12 | PXD007135 | Pride

Transcriptome profiling of Tasmanian Devil facial tumor (DFTD1) cell lines of 4 strains and the fibroblast cell line.

Project description:Purpose: To asses the transcriptome of 4 strains of the Tasmanian Devil facial tumor and one healthy fibroblast cell line. Methods: DFTD cells were grown from primary cell cultures derived from fine needle aspirates that have been collected from the wild. Total RNA from devil facial tumor strains 1-4 and the fibroblast was isolated from approximately 1 x 10^6 cells using QIAzol lysis reagent according to the manufacturer’s instructions (Qiagen). RNA-seq libraries were prepared with TruSeq Stranded mRNA LT sample preparation kit (Illumina) using Sciclone and Zephyr liquid handling robotics (PerkinElmer). The 5 libraries were pooled, diluted and sequenced on Illumina HiSeq 3000/4000 using 75 bp paired-end chemistry. Base calls provided by the Illumina Realtime Analysis software were converted into BAM format using Illumina2bam and demultiplexed using BamIndexDecoder. Paired-end reads were trimmed for adaptor sequences and filtered with the trimmomatic tool. Trimmed reads were aligned on the version 7.0 of the Tasmanian Devil with the STAR aligner. Counting of reads on annotated transcripts (Sarcophilus_harrisii.DEVIL7.0.90.gtf from Ensembl) was performed with featurecounts on fragments. The DESeq2 Biconductor library has been used for counts normalization and differential analysis between the transcriptomes of the four DFTD and fibroblast cell lines

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Passage of transmissible cancers in the Tasmanian devil is due to a dominant, shared peptide motif and a limited repertoire of MHC-I allotypes

Project description:Transmissible cancers are spread via the passage of malignant cells. The survival of the Tasmanian devil, the largest marsupial carnivore, is threatened by two independent transmissible cancers, devil facial tumour (DFT) 1 and devil facial tumour 2 (DFT2). To aid the development of a peptide vaccine and to interrogate how histocompatibility barriers can be overcome, we analysed the peptides bound to Major Histocompatibility Complex class I molecules from the Tasmanian devil and its transmissible tumours.

2021-02-08 | PXD020614 | Pride

Two of a kind: Transmissible Schwann cell cancers in the endangered Tasmanian devil.

Project description:Devil facial tumour disease 1 and 2 (DFT1 and DFT2) are two genetically distinct transmissible cancers endangering the survival of the Tasmanian devil (Sarcophilus harrisii). DFT1 first arose from a cell of the Schwann cell lineage, however, the tissue-of-origin of the recently discovered DFT2 cancer remains unknown. Here we have performed mRNA and protein expression analyses to show that variation in expression patterns between DFT1 and DFT2 tumours is low. Furthermore, DFT2 cells express a range of markers associated with Schwann cell differentiation, suggesting a similar tissue-of-origin to DFT1 tumours. These findings suggest that devils may be predisposed to transmissible cancers of Schwann cell origin. The emergence of these two unique cancers presents an unprecedented opportunity to gain insight into cancer development in animal species.

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Proteomic analysis of Tasmanian devil facial tumour disease

Project description:The Tasmanian devil is the only mammalian species harbouring two lineages of contagious cancer within its population. This dataset represents the proteomics analysis of DFT1, DFT2 and SALEM lines.

2021-09-09 | PXD021784 | Pride