Differentially expressed growth factors and cytokines drive phenotypic changes in transmissible cancers
Kathryn G Maskell1, Anna Schönbichler2, Andrew S Flies1
1Menzies Institute for Medical Research, University of Tasmania, Tasmania, Australia.
Introduction:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Insights
Researchers identified key proteins driving Tasmanian devil cancer cell plasticity and growth. These findings offer new therapeutic targets for conservation efforts against devil facial tumours.
Area of Science:
- Conservation biology
- Cancer cell biology
- Immunology
Background:
- Tasmanian devils face extinction due to two transmissible cancers: devil facial tumour 1 (DFT1) and DFT2.
- Phenotypic plasticity in DFT1 cells is a suspected mechanism for immune evasion and survival.
Purpose of the Study:
- To identify cytokines and growth factors influencing DFT cell plasticity.
- To investigate the role of these factors in DFT oncogenic properties and survival.
Main Methods:
- Differential expression analysis of cytokines and growth factors in DFT cell phenotypes.
- Investigating the effects of identified proteins on DFT cell proliferation, migration, and morphology.
Main Results:
- NRG1, IL16, TGFβ1, TGFβ2, and PDGFAA/AB proteins significantly impacted DFT cell behavior.
- PDGFR signaling enhanced proliferation and migration; TGFβ1/TGFβ2 induced EMT-like changes and increased migration while inhibiting proliferation.
Conclusions:
- Cytokine signaling intricately regulates DFT phenotypic plasticity, growth, and survival.
- Targeting implicated signaling pathways may lead to novel therapeutic interventions and vaccine development for Tasmanian devil conservation.
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