Menzies Institute for Medical Research, University of Tasmania, 17 Liverpool Street, Hobart, TAS, 7000, Australia.
Department of Veterinary Medicine, University of Cambridge, Cambridge, CB3 0ES, UK.
Cell Mol Life Sci. 2020 May;77(9):1847-1858. doi: 10.1007/s00018-019-03259-2. Epub 2019 Aug 2.
Devil facial tumour disease (DFTD) comprises two genetically distinct transmissible cancers (DFT1 and DFT2) endangering the survival of the Tasmanian devil (Sarcophilus harrisii) in the wild. DFT1 first arose from a cell of the Schwann cell lineage; however, the tissue-of-origin of the recently discovered DFT2 cancer is unknown. In this study, we compared the transcriptome and proteome of DFT2 tumours to DFT1 and normal Tasmanian devil tissues to determine the tissue-of-origin of the DFT2 cancer. Our findings demonstrate that DFT2 expresses a range of Schwann cell markers and exhibits expression patterns consistent with a similar origin to the DFT1 cancer. Furthermore, DFT2 cells express genes associated with the repair response to peripheral nerve damage. These findings suggest that devils may be predisposed to transmissible cancers of Schwann cell origin. The combined effect of factors such as frequent nerve damage from biting, Schwann cell plasticity and low genetic diversity may allow these cancers to develop on rare occasions. The emergence of two independent transmissible cancers from the same tissue in the Tasmanian devil presents an unprecedented opportunity to gain insight into cancer development, evolution and immune evasion in mammalian species.
恶魔面部肿瘤病(DFTD)由两种具有遗传差异的传染性癌症(DFT1 和 DFT2)组成,这两种癌症危及野生袋獾(Sarcophilus harrisii)的生存。DFT1 最初起源于施万细胞谱系的一个细胞;然而,最近发现的 DFT2 癌症的组织起源尚不清楚。在这项研究中,我们比较了 DFT2 肿瘤与 DFT1 和正常袋獾组织的转录组和蛋白质组,以确定 DFT2 癌症的组织起源。我们的研究结果表明,DFT2 表达了一系列施万细胞标记物,并表现出与 DFT1 癌症相似起源的表达模式。此外,DFT2 细胞表达与周围神经损伤修复反应相关的基因。这些发现表明,袋獾可能容易患上源自施万细胞的传染性癌症。频繁的咬伤导致的神经损伤、施万细胞可塑性和低遗传多样性等因素的综合作用,可能使这些癌症在极少数情况下得以发展。两种独立的传染性癌症从袋獾的同一组织中出现,为深入了解哺乳动物的癌症发展、进化和免疫逃逸提供了前所未有的机会。