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Quantitative Mass Spectrometric Profiling of Cancer-cell Proteomes Derived From Liquid and Solid Tumors
Published on: February 27, 2015
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Transcriptomic and proteomic profiling identifies feline fibrosarcoma as clinically amenable model for aggressive
Mikiyo Weber1, Daniel Fuchs1, Amiskwia Pöschel1
1Institute of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of Zurich, 8057 Zürich, Switzerland.
Neoplasia (New York, N.Y.)
|December 16, 2024
Summary
Feline fibrosarcomas (FSA) offer a valuable model for human disease. Molecular profiling reveals conserved targets and vulnerabilities, suggesting potential treatments like ATR and PARP inhibition for FSA.
Area of Science:
- Oncology
- Comparative Pathology
- Molecular Biology
Background:
- Fibrosarcomas (FSA) are aggressive tumors with poor treatment outcomes.
- Human FSA are rare, limiting clinical research and model development.
- Domestic cats develop frequent aggressive FSA, presenting a potential translational model.
Purpose of the Study:
- To perform comprehensive molecular characterization of feline fibrosarcomas (FSA) and matched normal tissues.
- To identify tumor-specific targets and conserved molecular pathways across species.
- To explore therapeutic vulnerabilities in feline FSA for potential human application.
Main Methods:
- Laser-capture microdissection, RNA sequencing, and liquid chromatography-tandem mass spectrometry.
- Comparative molecular profiling of 30 feline FSA and adjacent normal tissues.
- Bioinformatic analysis to identify differentially expressed genes and signaling pathways.
Main Results:
- Identified significant upregulation of EIF2, TP53, and MYC signaling in feline FSA.
- Discovered immune-related and neuronal pathways influencing tumor aggressiveness and immunosuppression.
- Found molecular similarities between feline, canine, and human FSA, with DNA repair pathway enrichment correlating with aggressive behavior.
Conclusions:
- Feline FSA exhibit molecular features relevant to human fibrosarcomas, supporting their use as a clinical model.
- Identified conserved tumor targets and vulnerabilities, including sensitivity to ATR and PARP inhibition.
- This molecular landscape provides a resource for developing novel diagnostic and therapeutic strategies for FSA in both species.
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