Proteomic profiling of canine fibrosarcoma and adjacent peritumoral tissue
Fibrosarcoma (FSA) are rare soft tissue tumors that display aggressive local behavior and invasive growth leading to high rates of tumor recurrence. While the low incidence in humans hampers detailed understanding of the disease, FSA are frequent in dogs and present potential models for the human co...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558622000835 |
| _version_ | 1797980734892277760 |
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| author | Erin Beebe Amiskwia Pöschel Laura Kunz Witold Wolski Zahra Motamed Daniela Meier Franco Guscetti Mirja C. Nolff Enni Markkanen |
| author_facet | Erin Beebe Amiskwia Pöschel Laura Kunz Witold Wolski Zahra Motamed Daniela Meier Franco Guscetti Mirja C. Nolff Enni Markkanen |
| author_sort | Erin Beebe |
| collection | DOAJ |
| description | Fibrosarcoma (FSA) are rare soft tissue tumors that display aggressive local behavior and invasive growth leading to high rates of tumor recurrence. While the low incidence in humans hampers detailed understanding of the disease, FSA are frequent in dogs and present potential models for the human condition. However, a lack of in-depth molecular characterization of FSA and unaffected peritumoral tissue (PTT) in both species impedes the translational potential of dogs. To address this shortcoming, we characterized canine FSA and matched skeletal muscle, adipose and connective tissue using laser-capture microdissection (LCM) and LC-MS/MS in 30 formalin-fixed paraffin embedded (FFPE) specimens. Principal component analysis of 3’530 different proteins detected across all samples clearly separates the four tissues, with several targets strongly differentiating tumor from all three PTTs. 25 proteins were exclusively found in tumor tissue in ≥80% of cases. Among these, CD68 (a macrophage marker), Optineurin (OPTN), Nuclear receptor coactivator 5 (NCOA5), RAP1GDS1 (Rap1 GTPase-GDP dissociation stimulator 1) and Stromal cell derived factor 2 like 1 (SDF2L1) were present in ≥90% of FSA. Protein expression across all FSA was highly homogeneous and characterized by MYC and TP53 signaling, hyperactive EIF2 and immune-related changes as well as strongly decreased oxidative phosphorylation and oxidative lipid metabolism. Finally, we demonstrate significant molecular homology between canine FSA and human soft-tissue sarcomas, emphasizing the relevance of studying canine FSA as a model for human FSA. In conclusion, we provide the first detailed overview of proteomic changes in FSA and surrounding PTT with relevance for the human disease. |
| first_indexed | 2024-04-11T05:59:37Z |
| format | Article |
| id | doaj.art-538b0bbfdad1451baa3134b8ae48a32f |
| institution | Directory Open Access Journal |
| issn | 1476-5586 |
| language | English |
| last_indexed | 2024-04-11T05:59:37Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-538b0bbfdad1451baa3134b8ae48a32f2022-12-22T04:41:47ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862023-01-0135100858Proteomic profiling of canine fibrosarcoma and adjacent peritumoral tissueErin Beebe0Amiskwia Pöschel1Laura Kunz2Witold Wolski3Zahra Motamed4Daniela Meier5Franco Guscetti6Mirja C. Nolff7Enni Markkanen8Institute of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of Zurich, 8057 Zürich, SwitzerlandInstitute of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of Zurich, 8057 Zürich, SwitzerlandFunctional Genomics Center Zürich, ETH Zürich/University of Zurich, 8057 Zürich, SwitzerlandFunctional Genomics Center Zürich, ETH Zürich/University of Zurich, 8057 Zürich, SwitzerlandInstitute of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of Zurich, 8057 Zürich, SwitzerlandZyto/Histo Diagnostik Labor Freienstein, 8427 Freienstein, SwitzerlandInstitute of Veterinary Pathology Vetsuisse Faculty, University of Zurich, 8057 Zürich, SwitzerlandSmall Animal Surgery, Tierspital Zürich, 8057 Zürich, Switzerland; Corresponding authors.Institute of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of Zurich, 8057 Zürich, Switzerland; Corresponding authors.Fibrosarcoma (FSA) are rare soft tissue tumors that display aggressive local behavior and invasive growth leading to high rates of tumor recurrence. While the low incidence in humans hampers detailed understanding of the disease, FSA are frequent in dogs and present potential models for the human condition. However, a lack of in-depth molecular characterization of FSA and unaffected peritumoral tissue (PTT) in both species impedes the translational potential of dogs. To address this shortcoming, we characterized canine FSA and matched skeletal muscle, adipose and connective tissue using laser-capture microdissection (LCM) and LC-MS/MS in 30 formalin-fixed paraffin embedded (FFPE) specimens. Principal component analysis of 3’530 different proteins detected across all samples clearly separates the four tissues, with several targets strongly differentiating tumor from all three PTTs. 25 proteins were exclusively found in tumor tissue in ≥80% of cases. Among these, CD68 (a macrophage marker), Optineurin (OPTN), Nuclear receptor coactivator 5 (NCOA5), RAP1GDS1 (Rap1 GTPase-GDP dissociation stimulator 1) and Stromal cell derived factor 2 like 1 (SDF2L1) were present in ≥90% of FSA. Protein expression across all FSA was highly homogeneous and characterized by MYC and TP53 signaling, hyperactive EIF2 and immune-related changes as well as strongly decreased oxidative phosphorylation and oxidative lipid metabolism. Finally, we demonstrate significant molecular homology between canine FSA and human soft-tissue sarcomas, emphasizing the relevance of studying canine FSA as a model for human FSA. In conclusion, we provide the first detailed overview of proteomic changes in FSA and surrounding PTT with relevance for the human disease.http://www.sciencedirect.com/science/article/pii/S1476558622000835Soft-tissue sarcomaComparative oncologyHuman fibrosarcomaLaser-capture microdissectionFibrosarcoma characterizationdog fibrosarcoma |
| spellingShingle | Erin Beebe Amiskwia Pöschel Laura Kunz Witold Wolski Zahra Motamed Daniela Meier Franco Guscetti Mirja C. Nolff Enni Markkanen Proteomic profiling of canine fibrosarcoma and adjacent peritumoral tissue Neoplasia: An International Journal for Oncology Research Soft-tissue sarcoma Comparative oncology Human fibrosarcoma Laser-capture microdissection Fibrosarcoma characterization dog fibrosarcoma |
| title | Proteomic profiling of canine fibrosarcoma and adjacent peritumoral tissue |
| title_full | Proteomic profiling of canine fibrosarcoma and adjacent peritumoral tissue |
| title_fullStr | Proteomic profiling of canine fibrosarcoma and adjacent peritumoral tissue |
| title_full_unstemmed | Proteomic profiling of canine fibrosarcoma and adjacent peritumoral tissue |
| title_short | Proteomic profiling of canine fibrosarcoma and adjacent peritumoral tissue |
| title_sort | proteomic profiling of canine fibrosarcoma and adjacent peritumoral tissue |
| topic | Soft-tissue sarcoma Comparative oncology Human fibrosarcoma Laser-capture microdissection Fibrosarcoma characterization dog fibrosarcoma |
| url | http://www.sciencedirect.com/science/article/pii/S1476558622000835 |
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