Gomesin peptides prevent proliferation and lead to the cell death of devil facial tumour disease cells.

The Tasmanian devil faces extinction due to devil facial tumour disease (DFTD), a highly transmittable clonal form of cancer without available treatment. In this study, we report the cell-autonomous antiproliferative and cytotoxic activities exhibited by the spider peptide gomesin (AgGom) and gomesin-like homologue (HiGom) in DFTD cells. Mechanistically, both peptides caused a significant reduction at G0/G1 phase, in correlation with an augmented expression of the cell cycle inhibitory proteins p53, p27, p21, necrosis, exacerbated generation of reactive oxygen species and diminished mitochondrial membrane potential, all hallmarks of cellular stress. The screening of a novel panel of AgGom-analogues revealed that, unlike changes in the hydrophobicity and electrostatic surface, the cytotoxic potential of the gomesin analogues in DFTD cells lies on specific arginine substitutions in the eight and nine positions and alanine replacement in three, five and 12 positions. In conclusion, the evidence supports gomesin as a potential antiproliferative compound against DFTD disease

New Insights into the Role of MHC Diversity in Devil Facial Tumour Disease

Devil facial tumour disease (DFTD) is a fatal contagious cancer that has decimated Tasmanian devil populations. The tumour has spread without invoking immune responses, possibly due to low levels of Major Histocompatibility Complex (MHC) diversity in Tasmanian devils. Animals from a region in north-western Tasmania have lower infection rates than those in the east of the state. This area is a genetic transition zone between sub-populations, with individuals from north-western Tasmania displaying greater diversity than eastern devils at MHC genes, primarily through MHC class I gene copy number variation. Here we test the hypothesis that animals that remain healthy and tumour free show predictable differences at MHC loci compared to animals that develop the disease

Genomic Restructuring in the Tasmanian Devil Facial Tumour: Chromosome Painting and Gene Mapping Provide Clues to Evolution of a Transmissible Tumour

Devil facial tumour disease (DFTD) is a fatal, transmissible malignancy that threatens the world's largest marsupial carnivore, the Tasmanian devil, with extinction. First recognised in 1996, DFTD has had a catastrophic effect on wild devil numbers, and intense research efforts to understand and contain the disease have since demonstrated that the tumour is a clonal cell line transmitted by allograft. We used chromosome painting and gene mapping to deconstruct the DFTD karyotype and determine the chromosome and gene rearrangements involved in carcinogenesis. Chromosome painting on three different DFTD tumour strains determined the origins of marker chromosomes and provided a general overview of the rearrangement in DFTD karyotypes. Mapping of 105 BAC clones by fluorescence in situ hybridisation provided a finer level of resolution of genome rearrangements in DFTD strains. Our findings demonstrate that only limited regions of the genome, mainly chromosomes 1 and X, are rearranged in DFTD. Regions rearranged in DFTD are also highly rearranged between different marsupials. Differences between strains are limited, reflecting the unusually stable nature of DFTD. Finally, our detailed maps of both the devil and tumour karyotypes provide a physical framework for future genomic investigations into DFTD

Spawning-related fungal infection of golden galaxias Galaxias auratus (Galaxiidae)

The occurrence of golden galaxias Galaxias auratus with dermal fungal lesions in two populations was effectively modelled by the progression of gonadal stages of development. Skin lesions were found to be characteristic of fungal dermatitis and a Saprolegnia sp. was identified as the causative agent. Infection is probably linked to spawning-related factors and it is probable that saprolegniasis is associated with seasonal mortality. © 2007 The Fisheries Society of the British Isles

ERBB3: A potential serum biomarker for early detection and therapeutic target for devil facial tumour 1 (DFT1)

Devil Facial Tumour 1 (DFT1) is one of two transmissible neoplasms of Tasmanian devils (Sarcophilus harrisii) predominantly affecting their facial regions. DFT1’s cellular origin is that of Schwann cell lineage where lesions are evident macroscopically late in the disease. Conversely, the pre-clinical timeframe from cellular transmission to appearance of DFT1 remains uncertain demonstrating the importance of an effective pre-clinical biomarker. We show that ERBB3, a marker expressed normally by the developing neural crest and Schwann cells, is immunohistohemically expressed by DFT1, therefore the potential of ERBB3 as a biomarker was explored. Under the hypothesis that serum ERBB3 levels may increase as DFT1 invades local and distant tissues our pilot study determined serum ERBB3 levels in normal Tasmanian devils and Tasmanian devils with DFT1. Compared to the baseline serum ERBB3 levels in unaffected Tasmanian devils, Tasmanian devils with DFT1 showed significant elevation of serum ERBB3 levels. Interestingly Tasmanian devils with cutaneous lymphoma (CL) also showed elevation of serum ERBB3 levels when compared to the baseline serum levels of Tasmanian devils without DFT1. Thus, elevated serum ERBB3 levels in otherwise healthy looking devils could predict possible DFT1 or CL in captive or wild devil populations and would have implications on the management, welfare and survival of Tasmanian devils. ERBB3 is also a therapeutic target and therefore the potential exists to consider modes of administration that may eradicate DFT1 from the wild

Dental Pulp Stem Cells - Exploration in a Novel Animal Model: the Tasmanian Devil (Sarcophilus harrisii)

Dental pulp stem cells (DPSC) are a heterogeneous population of highly proliferative stem cells located in the soft inner pulp tissue of the tooth. Demonstrated to have an affinity for neural differentiation, DPSC have been reported to generate functional Schwann cells (SC) through in vitro differentiation. Both DPSC and SC have neural crest origins, recently a significant population of DPSC have been reported to derive from peripheral nerve-associated glia. The predisposition DPSC have towards the SC lineage is not only a very useful tool for neural regenerative therapies in the medical field, it also holds great promise in the veterinary field. Devil Facial Tumour (DFT) is a clonally transmissible cancer of SC origin responsible for devastating wild populations of the Tasmanian devil. Very few studies have investigated the healthy Tasmanian devil SC (tdSC) for comparative studies between tdSC and DFT cells, and the development and isolation of a tdSC population is yet to be undertaken. A Tasmanian devil DPSC model offers a promising new outlook for DFT research, and the link between SC and DPSC may provide a potential explanation as to how a cancerous SC initially arose in a single Tasmanian devil to then go on to infect others as a parasitic clonal cell line. In this review we explore the current role of DPSC in human regenerative medicine, provide an overview of the Tasmanian devil and the devastating effect of DFT, and highlight the promising potential DPSC techniques pose for DFT research and our current understanding of DFT.Chelsea M. Graham, Karlea L. Kremer, Simon A. Koblar, Monica A. Hamilton-Bruce, Stephen B. Pyecrof