Investigation of the Epithelial to Mesenchymal Transition (EMT) Process in Equine Papillomavirus-2 (EcPV-2)-Positive Penile Squamous Cell Carcinomas
Equine penile squamous cell carcinoma (epSCC) is the most frequent tumor of the external male genitalia, representing 67.5% of equine genital cancers. epSCC is associated with papilloma virus (PV) infection and has been recently proposed as a model for human PV-induced squamous cell carcinomas. It h...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-09-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/22/19/10588 |
_version_ | 1797516309247819776 |
---|---|
author | Federico Armando Samanta Mecocci Virginia Orlandi Ilaria Porcellato Katia Cappelli Luca Mechelli Chiara Brachelente Marco Pepe Rodolfo Gialletti Alessandro Ghelardi Benedetta Passeri Elisabetta Razzuoli |
author_facet | Federico Armando Samanta Mecocci Virginia Orlandi Ilaria Porcellato Katia Cappelli Luca Mechelli Chiara Brachelente Marco Pepe Rodolfo Gialletti Alessandro Ghelardi Benedetta Passeri Elisabetta Razzuoli |
author_sort | Federico Armando |
collection | DOAJ |
description | Equine penile squamous cell carcinoma (epSCC) is the most frequent tumor of the external male genitalia, representing 67.5% of equine genital cancers. epSCC is associated with papilloma virus (PV) infection and has been recently proposed as a model for human PV-induced squamous cell carcinomas. It has already been suggested that epSCC might undergo epithelial-to-mesenchymal transition (EMT). This work aims to investigate in detail this process and the possible role of PV oncoproteins in epSCC. For this purpose, 18 penile SCCs were retrospectively selected and tested for both EcPV2 presence and oncoproteins (EcPV2 E6 and EcPV2 E7) expression. Moreover, immunohistochemical EMT characterization was carried out by analyzing the main epithelial markers (E-cadherin, β-catenin, and pan-cytokeratin AE3/AE1), the main mesenchymal markers (N-cadherin and vimentin), and the main EMT-related transcription factors (TWIST-1, ZEB-1). PCR analysis was positive for EcPV2 in 16 out of 18 samples. EMT was investigated in epSCC positive for EcPV2. The immunohistochemistry results suggested the presence of EMT processes in the neoplastic cells at the tumor invasive front. Moreover, the significant upregulation of <i>RANKL</i>, together with <i>BCATN1</i>, <i>LEF1</i>, and <i>FOSL1</i> genes, might suggest a canonical Wnt pathway activation, similarly to what is reported in human penile squamous cell carcinomas |
first_indexed | 2024-03-10T06:59:26Z |
format | Article |
id | doaj.art-f023d85975ad446db783e899bb91ff8f |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-10T06:59:26Z |
publishDate | 2021-09-01 |
publisher | MDPI AG |
record_format | Article |
series | International Journal of Molecular Sciences |
spelling | doaj.art-f023d85975ad446db783e899bb91ff8f2023-11-22T16:12:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122191058810.3390/ijms221910588Investigation of the Epithelial to Mesenchymal Transition (EMT) Process in Equine Papillomavirus-2 (EcPV-2)-Positive Penile Squamous Cell CarcinomasFederico Armando0Samanta Mecocci1Virginia Orlandi2Ilaria Porcellato3Katia Cappelli4Luca Mechelli5Chiara Brachelente6Marco Pepe7Rodolfo Gialletti8Alessandro Ghelardi9Benedetta Passeri10Elisabetta Razzuoli11Department of Pathology, University of Veterinary Medicine Hannover, Bünteweg 17, 30559 Hannover, GermanyDepartment of Veterinary Medicine, University of Perugia, 06126 Perugia, ItalyDepartment of Veterinary Science, University of Parma, 43121 Parma, ItalyDepartment of Veterinary Medicine, University of Perugia, 06126 Perugia, ItalyDepartment of Veterinary Medicine, University of Perugia, 06126 Perugia, ItalyDepartment of Veterinary Medicine, University of Perugia, 06126 Perugia, ItalyDepartment of Veterinary Medicine, University of Perugia, 06126 Perugia, ItalyDepartment of Veterinary Medicine, University of Perugia, 06126 Perugia, ItalyDepartment of Veterinary Medicine, University of Perugia, 06126 Perugia, ItalyAzienda Usl Toscana Nord-Ovest, UOC Ostetricia e Ginecologia, Ospedale Apuane, 54100 Massa, ItalyDepartment of Veterinary Science, University of Parma, 43121 Parma, ItalyNational Reference Center of Veterinary and Comparative Oncology (CEROVEC), 16129 Genova, ItalyEquine penile squamous cell carcinoma (epSCC) is the most frequent tumor of the external male genitalia, representing 67.5% of equine genital cancers. epSCC is associated with papilloma virus (PV) infection and has been recently proposed as a model for human PV-induced squamous cell carcinomas. It has already been suggested that epSCC might undergo epithelial-to-mesenchymal transition (EMT). This work aims to investigate in detail this process and the possible role of PV oncoproteins in epSCC. For this purpose, 18 penile SCCs were retrospectively selected and tested for both EcPV2 presence and oncoproteins (EcPV2 E6 and EcPV2 E7) expression. Moreover, immunohistochemical EMT characterization was carried out by analyzing the main epithelial markers (E-cadherin, β-catenin, and pan-cytokeratin AE3/AE1), the main mesenchymal markers (N-cadherin and vimentin), and the main EMT-related transcription factors (TWIST-1, ZEB-1). PCR analysis was positive for EcPV2 in 16 out of 18 samples. EMT was investigated in epSCC positive for EcPV2. The immunohistochemistry results suggested the presence of EMT processes in the neoplastic cells at the tumor invasive front. Moreover, the significant upregulation of <i>RANKL</i>, together with <i>BCATN1</i>, <i>LEF1</i>, and <i>FOSL1</i> genes, might suggest a canonical Wnt pathway activation, similarly to what is reported in human penile squamous cell carcinomashttps://www.mdpi.com/1422-0067/22/19/10588EMTHorseEcPV2penile squamous cell carcinomawnt/βcatenin pathwayRANKL |
spellingShingle | Federico Armando Samanta Mecocci Virginia Orlandi Ilaria Porcellato Katia Cappelli Luca Mechelli Chiara Brachelente Marco Pepe Rodolfo Gialletti Alessandro Ghelardi Benedetta Passeri Elisabetta Razzuoli Investigation of the Epithelial to Mesenchymal Transition (EMT) Process in Equine Papillomavirus-2 (EcPV-2)-Positive Penile Squamous Cell Carcinomas International Journal of Molecular Sciences EMT Horse EcPV2 penile squamous cell carcinoma wnt/βcatenin pathway RANKL |
title | Investigation of the Epithelial to Mesenchymal Transition (EMT) Process in Equine Papillomavirus-2 (EcPV-2)-Positive Penile Squamous Cell Carcinomas |
title_full | Investigation of the Epithelial to Mesenchymal Transition (EMT) Process in Equine Papillomavirus-2 (EcPV-2)-Positive Penile Squamous Cell Carcinomas |
title_fullStr | Investigation of the Epithelial to Mesenchymal Transition (EMT) Process in Equine Papillomavirus-2 (EcPV-2)-Positive Penile Squamous Cell Carcinomas |
title_full_unstemmed | Investigation of the Epithelial to Mesenchymal Transition (EMT) Process in Equine Papillomavirus-2 (EcPV-2)-Positive Penile Squamous Cell Carcinomas |
title_short | Investigation of the Epithelial to Mesenchymal Transition (EMT) Process in Equine Papillomavirus-2 (EcPV-2)-Positive Penile Squamous Cell Carcinomas |
title_sort | investigation of the epithelial to mesenchymal transition emt process in equine papillomavirus 2 ecpv 2 positive penile squamous cell carcinomas |
topic | EMT Horse EcPV2 penile squamous cell carcinoma wnt/βcatenin pathway RANKL |
url | https://www.mdpi.com/1422-0067/22/19/10588 |
work_keys_str_mv | AT federicoarmando investigationoftheepithelialtomesenchymaltransitionemtprocessinequinepapillomavirus2ecpv2positivepenilesquamouscellcarcinomas AT samantamecocci investigationoftheepithelialtomesenchymaltransitionemtprocessinequinepapillomavirus2ecpv2positivepenilesquamouscellcarcinomas AT virginiaorlandi investigationoftheepithelialtomesenchymaltransitionemtprocessinequinepapillomavirus2ecpv2positivepenilesquamouscellcarcinomas AT ilariaporcellato investigationoftheepithelialtomesenchymaltransitionemtprocessinequinepapillomavirus2ecpv2positivepenilesquamouscellcarcinomas AT katiacappelli investigationoftheepithelialtomesenchymaltransitionemtprocessinequinepapillomavirus2ecpv2positivepenilesquamouscellcarcinomas AT lucamechelli investigationoftheepithelialtomesenchymaltransitionemtprocessinequinepapillomavirus2ecpv2positivepenilesquamouscellcarcinomas AT chiarabrachelente investigationoftheepithelialtomesenchymaltransitionemtprocessinequinepapillomavirus2ecpv2positivepenilesquamouscellcarcinomas AT marcopepe investigationoftheepithelialtomesenchymaltransitionemtprocessinequinepapillomavirus2ecpv2positivepenilesquamouscellcarcinomas AT rodolfogialletti investigationoftheepithelialtomesenchymaltransitionemtprocessinequinepapillomavirus2ecpv2positivepenilesquamouscellcarcinomas AT alessandroghelardi investigationoftheepithelialtomesenchymaltransitionemtprocessinequinepapillomavirus2ecpv2positivepenilesquamouscellcarcinomas AT benedettapasseri investigationoftheepithelialtomesenchymaltransitionemtprocessinequinepapillomavirus2ecpv2positivepenilesquamouscellcarcinomas AT elisabettarazzuoli investigationoftheepithelialtomesenchymaltransitionemtprocessinequinepapillomavirus2ecpv2positivepenilesquamouscellcarcinomas |