ORIGINAL RESEARCH article
Front. Vet. Sci.
Sec. Oncology in Veterinary Medicine
This article is part of the Research TopicPrecision Diagnosis and Targeted Therapies in Companion Animal OncologyView all 6 articles
Expression patterns of fibroblast activation protein and extra-domain B fibronectin in canine malignant tumors
Provisionally accepted
Silvia Dell'Aere1*
Elisa Maria Gariboldi1
Alessandra Ubiali1
Roberta Ferrari1
Luigi Auletta1
Matilde Bocci2
Andrea Galbiati2
Ettore Gilardoni2Giulia Rotta2Valentina Balbi1
Gaia Beatrice Maria Bianchi1
Alessandra Verdi1Dario Neri3,4
Samuele Cazzamalli2
Damiano Stefanello1
Paola Roccabianca1- 1Department of Veterinary Medicine and Animal Sciences, University of Milan, Milan, Italy
- 2R&D department, Philochem AG, Otelfingen, Switzerland
- 3Philogen SpA, Siena, Italy
- 4Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, Zurich, Switzerland
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Fibroblast activation protein (FAP) is involved in the extracellular matrix (ECM) remodeling and wound healing. Absent in most adult tissues, it is overexpressed by neoplastic cells and/or cancer-associated fibroblasts (CAFs) in several human malignancies. The extra Domain-B of fibronectin (EDB+FN) is a splice variant of fibronectin involved in angiogenesis and tissue remodeling, overexpressed by CAFs and cancer-associated vessels (CAVs) in many aggressive human tumors. This study aims to investigate FAP and EDB+FN expressions in canine tumors and assess their potential as druggable targets in animal patients. FAP and EDB+FN expression was assessed by immunohistochemistry on 88 canine tumors, including Soft Tissue Sarcomas [STS], Osteosarcomas [OSA], Hemangiosarcomas [HSA], Apocrine Gland Anal Sac Adenocarcinomas [AGASAC], Mast Cell Tumors [MCT], Lymphomas, and Melanomas, using polyclonal and monoclonal anti-FAP and the L19 anti-EDB antibodies. Expression distribution and intensity were semi-quantitatively scored in neoplastic cells, CAFs, CAVs, and stroma. FAP was variably expressed in neoplastic cells (79/88), CAFs (79/88), and CAVs (82/88) across all tumor types, but mostly in AGASACs, STSs, and MCTs. The monoclonal antibody presented greater specificity. EDB+FN expression was less present across tumor types, mostly with a vascular staining pattern. Labelling was most intense and consistent in the neoplastic cells, CAFs, and CAVs of melanomas, and to a lesser extent in AGASAC and STS. STS, AGASAC, and MCT could be candidates for FAP-targeted strategies, while melanomas are the most promising for EDB+FN-directed therapies. These results support FAP and EDB+FN as targets worth investigating for clinical applications in animal patients.
Keywords: canine tumor, EDB, extra domain B, FAP, fibroblast activation protein, fibronectin, Melanoma, Sarcoma
Received: 07 Oct 2025; Accepted: 15 Dec 2025.
Copyright: © 2025 Dell'Aere, Gariboldi, Ubiali, Ferrari, Auletta, Bocci, Galbiati, Gilardoni, Rotta, Balbi, Bianchi, Verdi, Neri, Cazzamalli, Stefanello and Roccabianca. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Silvia Dell'Aere
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