o:1794 Tumor Cell Plasticity in Equine Papillomavirus-Positive Versus-Negative Squamous Cell Carcinoma of the Head and Neck en 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 1552099 10.3390/pathogens11020266 2023-07-03T14:30:09.516Z 44 yes 46 Carina Strohmayer University of Veterinary Medicine Vienna 0000-0002-6552-357X Sabine Brandt University of Veterinary Medicine Vienna person 0000-0002-3837-3422 Sibylle Kneissl University of Veterinary Medicine Vienna person 0000-0001-9588-4715 Torben Redmer University of Veterinary Medicine Vienna person 0000-0002-0050-9478 Christiane Weissenbacher-Lang University of Veterinary Medicine person 0000-0002-1527-7593 Christoph Jindra University of Veterinary Medicine Vienna person Ingrid Walter University of Veterinary Medicine Vienna person 0000-0002-5038-188X Andrea Klang University of Veterinary Medicine Vienna person Stefan Kummer University of Veterinary Medicine Vienna person 0000-0002-0746-1403 application/pdf 6741361 https://phaidra.vetmeduni.ac.at/o:1794 no yes 16 70 1552253 Pathogens 20 11 2 MDPI 2022