https://phaidra.vetmeduni.ac.at/o:1794 Tumor Cell Plasticity in Equine Papillomavirus-Positive Versus-Negative Squamous Cell Carcinoma of the Head and Neck Strohmayer, Carina Carina Strohmayer 0000-0002-6552-357X University of Veterinary Medicine Vienna Brandt, Sabine Sabine Brandt 0000-0002-3837-3422 University of Veterinary Medicine Vienna Kneissl, Sibylle Sibylle Kneissl 0000-0001-9588-4715 University of Veterinary Medicine Vienna Redmer, Torben Torben Redmer 0000-0002-0050-9478 University of Veterinary Medicine Vienna Weissenbacher-Lang, Christiane Christiane Weissenbacher-Lang 0000-0002-1527-7593 University of Veterinary Medicine Jindra, Christoph Christoph Jindra University of Veterinary Medicine Vienna Walter, Ingrid Ingrid Walter 0000-0002-5038-188X University of Veterinary Medicine Vienna Klang, Andrea Andrea Klang University of Veterinary Medicine Vienna Kummer, Stefan Stefan Kummer 0000-0002-0746-1403 University of Veterinary Medicine Vienna MDPI text eng Squamous cell carcinoma of the head and neck (HNSCC) is a common malignant tumor in humans and animals. In humans, papillomavirus (PV)-induced HNSCCs have a better prognosis than papillomavirus-unrelated HNSCCs. The ability of tumor cells to switch from epithelial to mesenchymal, endothelial, or therapy-resistant stem-cell-like phenotypes promotes disease progression and metastasis. In equine HNSCC, PV-association and tumor cell phenotype switching are poorly understood. We screened 49 equine HNSCCs for equine PV (EcPV) type 2, 3 and 5 infection. Subsequently, PV-positive versus -negative lesions were analyzed for expression of selected epithelial (keratins, β-catenin), mesenchymal (vimentin), endothelial (COX-2), and stem-cell markers (CD271, CD44) by immunohistochemistry (IHC) and immunofluorescence (IF; keratins/vimentin, CD44/CD271 double-staining) to address tumor cell plasticity in relation to PV infection. Only EcPV2 PCR scored positive for 11/49 equine HNSCCs. IHC and IF from 11 EcPV2-positive and 11 EcPV2-negative tumors revealed epithelial-to-mesenchymal transition events, with vimentin-positive cells ranging between <10 and >50%. CD44- and CD271-staining disclosed the intralesional presence of infiltrative tumor cell fronts and double-positive tumor cell subsets independently of the PV infection status. Our findings are indicative of (partial) epithelial-mesenchymal transition events giving rise to hybrid epithelial/mesenchymal and stem-cell-like tumor cell phenotypes in equine HNSCCs and suggest CD44 and CD271 as potential malignancy markers that merit to be further explored in the horse. Cancer Stem-Cells; Epithelial-Mesenchymal Transition; Cadherin Down-Regulation; Beta-Catenin; Nuclear Translocation; Initiating Cells; Expression; Dna; Metastasis; Phenotype http://creativecommons.org/licenses/by/4.0/ https://phaidra.vetmeduni.ac.at/api/object/o:1794/download 10.3390/pathogens11020266 https://phaidra.vetmeduni.ac.at/o:605 application/pdf Pathogens 11(2) (2022) Pathogens 11 2 6.43 MB 2022