phaidra.vetmeduni.ac.at o:1794 DOI 10.3390/pathogens11020266 Tumor Cell Plasticity in Equine Papillomavirus-Positive Versus-Negative Squamous Cell Carcinoma of the Head and Neck 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. eng Cancer Stem-Cells; Epithelial-Mesenchymal Transition; Cadherin Down-Regulation; Beta-Catenin; Nuclear Translocation; Initiating Cells; Expression; Dna; Metastasis; Phenotype 2023-10-25T12:31:16.929Z LOMv1.0 Author BEGIN:VCARD VERSION:3.0 N:Strohmayer;Carina; FN:Carina Strohmayer X-ORCID:https://orcid.org/0000-0002-6552-357X END:VCARD BEGIN:VCARD VERSION:3.0 N:Brandt;Sabine; FN:Sabine Brandt X-ORCID:https://orcid.org/0000-0002-3837-3422 END:VCARD BEGIN:VCARD VERSION:3.0 N:Kneissl;Sibylle; FN:Sibylle Kneissl X-ORCID:https://orcid.org/0000-0001-9588-4715 END:VCARD BEGIN:VCARD VERSION:3.0 N:Redmer;Torben; FN:Torben Redmer X-ORCID:https://orcid.org/0000-0002-0050-9478 END:VCARD BEGIN:VCARD VERSION:3.0 N:Weissenbacher-Lang;Christiane; FN:Christiane Weissenbacher-Lang X-ORCID:https://orcid.org/0000-0002-1527-7593 END:VCARD BEGIN:VCARD VERSION:3.0 N:Jindra;Christoph; FN:Christoph Jindra END:VCARD BEGIN:VCARD VERSION:3.0 N:Walter;Ingrid; FN:Ingrid Walter X-ORCID:https://orcid.org/0000-0002-5038-188X END:VCARD BEGIN:VCARD VERSION:3.0 N:Klang;Andrea; FN:Andrea Klang END:VCARD BEGIN:VCARD VERSION:3.0 N:Kummer;Stefan; FN:Stefan Kummer X-ORCID:https://orcid.org/0000-0002-0746-1403 END:VCARD https://w3id.org/kim/hcrt/scheme https://w3id.org/kim/hcrt/text Textdokument Text LOMv1.0 yes https://creativecommons.org/licenses/by/4.0 application/pdf 6741361 https://phaidra.vetmeduni.ac.at/o:1794 https://phaidra.vetmeduni.ac.at/api/object/o:1794/thumbnail LOMv1.0 discipline