Maskell Kathryn G, Schönbichler Anna, Flies Andrew S, Patchett Amanda L
Menzies Institute for Medical Research, University of Tasmania, Tasmania, Australia.
Institute for Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria.
Discov Immunol. 2025 Jul 12;4(1):kyaf011. doi: 10.1093/discim/kyaf011. eCollection 2025.
The Tasmanian devil is threatened by two deadly transmissible Schwann cell cancers. A vaccine to protect Tasmanian devils from both devil facial tumour 1 (DFT1) and devil facial tumour 2 (DFT2), and improved understanding of the cancer cell biology, could support improved conservation actions.
Previous transcriptomic analysis has implicated phenotypic cellular plasticity as a potential immune escape and survival mechanism of DFT1 cells. This phenotypic plasticity facilitates transition from a myelinating Schwann cell to a repair Schwann cell phenotype that exhibits mesenchymal characteristics. Here, we have identified cytokines and growth factors differentially expressed across DFT cell phenotypes and investigated their role in driving phenotypic plasticity and oncogenic properties of DFT cells.
Our results show that NRG1, IL16, TGFβ1, TGFβ2, and PDGFAA/AB proteins have significant and distinct effects on the proliferation rate, migratory capacity and/or morphology of DFT cells. Specifically, PDGFR signalling, induced by PDGFAA/AB, was a strong enhancer of cell proliferation and migration, while TGFβ1 and TGFβ2 induced epithelial-mesenchymal transition (EMT)-like changes, inhibited proliferation and increased migratory capacity.
These findings suggest complex interactions between cytokine signalling, phenotypic plasticity, growth and survival of DFTs. Signalling pathways implicated in the propagation of DFT are potential targets for therapeutic intervention and vaccine development for Tasmanian devil conservation.
袋獾受到两种致命的可传播雪旺氏细胞瘤的威胁。一种能保护袋獾免受袋獾面部肿瘤1型（DFT1）和袋獾面部肿瘤2型（DFT2）侵害的疫苗，以及对癌细胞生物学的深入了解，有助于改进保护措施。
先前的转录组分析表明，细胞表型可塑性是DFT1细胞潜在的免疫逃逸和生存机制。这种表型可塑性促进了从有髓雪旺氏细胞向具有间充质特征的修复雪旺氏细胞表型的转变。在此，我们鉴定了DFT细胞表型中差异表达的细胞因子和生长因子，并研究了它们在驱动DFT细胞表型可塑性和致癌特性中的作用。
我们的结果表明，NRG1、IL16、TGFβ1、TGFβ2和PDGFAA/AB蛋白对DFT细胞的增殖率、迁移能力和/或形态具有显著且不同的影响。具体而言，由PDGFAA/AB诱导的PDGFR信号传导是细胞增殖和迁移的强大增强剂，而TGFβ1和TGFβ2诱导上皮-间质转化（EMT）样变化，抑制增殖并增加迁移能力。
这些发现表明细胞因子信号传导、表型可塑性、DFT的生长和存活之间存在复杂的相互作用。与DFT传播相关的信号通路是袋獾保护治疗干预和疫苗开发的潜在靶点。
