Armando Federico, Godizzi Francesco, Razzuoli Elisabetta, Leonardi Fabio, Angelone Mario, Corradi Attilio, Meloni Daniela, Ferrari Luca, Passeri Benedetta
Pathology Unit, Department of Veterinary Science, University of Parma, Strada del Taglio 10, 43126 Parma, Italy.
Department of Veterinary Science (DIMEVET), University of Milan, Via dell'Università 6, 26900 Lodi, Italy.
Animals (Basel). 2020 Dec 7;10(12):2318. doi: 10.3390/ani10122318.
Squamous cell carcinoma (SCC) is one of the most frequent tumors of skin and muco-cutaneous junctions in the horse. Equine papillomavirus type 2 (EcPV2) has been detected in equine SCC of the oral tract and genitals, and recently also in the larynx. As human squamous cell carcinoma of the larynx (SCCL), it is strongly etiologically associated with high-risk papillomavirus (h-HPV) infection. This study focuses on tumor cells behavior in a naturally occurring tumor that can undergo the so-called epithelial to mesenchymal transition (EMT). A SCCL in a horse was investigated by immunohistochemistry using antibodies against E-cadherin, pan-cytokeratin AE3/AE1, β-catenin, N-cadherin, vimentin, ZEB-1, TWIST, and HIF-1α. EcPV2 DNA detection and expression of oncogenes in SCC were investigated. A cadherin switch and an intermediate filaments rearrangement within primary site tumor cells together with the expression of the EMT-related transcription factors TWIST-1, ZEB-1, and HIF-1α were observed. DNA obtained from the tumor showed EcPV2 positivity, with E2 gene disruption and E6 gene dysregulation. The results suggest that equine SCCL might be a valuable model for studying EMT and the potential interactions between EcPV2 oncoproteins and the EMT process in SCCL.
鳞状细胞癌(SCC)是马皮肤和黏膜皮肤交界处最常见的肿瘤之一。在马口腔和生殖器的SCC中已检测到2型马乳头瘤病毒(EcPV2),最近在喉部也检测到了。与人类喉鳞状细胞癌(SCCL)一样,它在病因上与高危乳头瘤病毒(h-HPV)感染密切相关。本研究聚焦于一种自然发生的肿瘤中肿瘤细胞的行为,该肿瘤可发生所谓的上皮-间质转化(EMT)。使用抗E-钙黏蛋白、泛细胞角蛋白AE3/AE1、β-连环蛋白、N-钙黏蛋白、波形蛋白、锌指E盒结合蛋白1(ZEB-1)、TWIST和缺氧诱导因子-1α(HIF-1α)的抗体,通过免疫组织化学对一匹马的SCCL进行了研究。研究了SCC中EcPV2 DNA检测和癌基因表达情况。观察到原发部位肿瘤细胞中钙黏蛋白转换和中间丝重排,以及EMT相关转录因子TWIST-1、ZEB-1和HIF-1α的表达。从肿瘤中获得的DNA显示EcPV2呈阳性,伴有E2基因破坏和E6基因失调。结果表明,马SCCL可能是研究EMT以及EcPV2癌蛋白与SCCL中EMT过程之间潜在相互作用的有价值模型。