Abstract
Contagious cancers are a rare pathogenic phenomenon in which cancer cells gain the ability to spread between genetically distinct hosts. Nine examples have been identified across marine bivalves, dogs and Tasmanian devils, but the Tasmanian devil is the only mammalian species known to have given rise to two distinct lineages of contagious cancer, termed Devil Facial Tumour 1 (DFT1) and 2 (DFT2). Remarkably, DFT1 and DFT2 arose independently from the same cell type, a Schwann cell, and while their ultra-structural features are highly similar they exhibit variation in their mutational signatures and infection dynamics. As such, DFT1 and DFT2 provide a unique framework for investigating how a common progenitor cell can give rise to distinct contagious cancers. Using a proteomics approach, we show that DFT1 and DFT2 are derived from Schwann cells in different differentiation states, with DFT2 carrying a molecular signature of a less well differentiated Schwann cell. Under inflammatory signals DFT1 and DFT2 have different gene expression profiles, most notably involving Schwann cell markers of differentiation, reflecting the influence of their distinct origins. Further, DFT2 cells express immune cell markers typically expressed during nerve repair, consistent with an ability to manipulate their extracellular environment, facilitating the cell's ability to transmit between individuals. The emergence of two contagious cancers in the Tasmanian devil suggests that the inherent plasticity of Schwann cells confers a vulnerability to the formation of contagious cancers.
Highlights
Identifying the origin of a pathogen is key to predicting its evolutionary trajectory, the mechanisms of emergence and developing appropriate disease management strategies
Other myelin associated proteins significantly overexpressed in Devil Facial Tumour 1 (DFT1) relative to fibroblasts include Early Growth Response protein 2 (EGR2)[31] (2.10 fold, p = 4.67 x10-3), Myelin Associated Glycoprotein (MAG) [32] (5.56 fold, p = 3.51 x10-6) and Uridine Diphosphate Glycosyltransferase 8 (UGT8) [33] (4.74 fold, p = 1.78 x10-4) (S1 Table)
The independent emergence of DFT1 and Devil Facial Tumour 2 (DFT2) from Schwann cells provides a unique opportunity to define how the characteristics of a progenitor cell can shape the phenotype and Progenitor differentiation state drives contagious cancer phenotype grown in normal cell culture media, γ indicates cells treated for 16 hours with recombinant devil IFNγ
Summary
Identifying the origin of a pathogen is key to predicting its evolutionary trajectory, the mechanisms of emergence and developing appropriate disease management strategies. Contagious cancers can emerge when malignant cells gain the ability to spread between genetically distinct hosts and propagate through a population in a manner akin to a parasite [1]. These cancers present a significant health risk to their hosts and a conservation issue when circulating in vulnerable populations. In 2014, grossly identical facial tumours were identified which have a distinct histology, which lacked expression of PRX [6] This new tumour was termed DFT2, and its prevalence and range is increasing [7]. All evidence indicates that DFT1 and DFT2 are genetically distinct tumours which have emerged independently of one another [6,8]
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