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International journal of molecular sciences2021; 22(19); 10588; doi: 10.3390/ijms221910588

Investigation of the Epithelial to Mesenchymal Transition (EMT) Process in Equine Papillomavirus-2 (EcPV-2)-Positive Penile Squamous Cell Carcinomas.

Abstract: 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 , together with , , and genes, might suggest a canonical Wnt pathway activation, similarly to what is reported in human penile squamous cell carcinomas.
Publication Date: 2021-09-30 PubMed ID: 34638929PubMed Central: PMC8508821DOI: 10.3390/ijms221910588Google Scholar: Lookup
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  • Journal Article

Summary

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This study explores the process of Epithelial to Mesenchymal Transition (EMT) in equine penile squamous cell carcinoma (epSCC), a prevalent tumor in male horse genitalia linked to papillomavirus infection. The researchers further investigate the potential role of papillomavirus proteins in this transition, revealing some possible similarities to human papillomavirus-induced carcinomas.

Background and Purpose

  • Equine penile squamous cell carcinoma (epSCC) is a common tumor in the external male genitalia in horses, accounting for approximately 67.5% of genital cancers in these animals.
  • This type of cancer is often associated with a papillomavirus (PV) infection, and there is ongoing research to understand this relationship better.
  • Previous research suggested that a process known as epithelial-to-mesenchymal transition (EMT) might occur in epSCC. This study aimed to delve deeper into understanding the EMT in epSCC and to assess the potential role of PV proteins in this process.

Research Methodology

  • The researchers selected 18 cases of penile SCC and tested them for the presence of EcPV2, a strain of the equine papillomavirus, and the expression of EcPV2 E6 and EcPV2 E7 proteins, which are oncogenic (cancer-causing).
  • They also carried out immunohistochemical EMT characterization, analyzing 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).

Findings of the Study

  • PCR analysis revealed that 16 out of the 18 samples were positive for EcPV2.
  • Via immunohistochemistry, the researchers detected EMT processes in the cells at the invasive front of the tumor in epSCC samples that tested positive for EcPV2.
  • The significant upregulation of specific genes suggests that a canonical Wnt pathway might be activated. This finding is interesting because similar activation has been reported in human penile squamous cell carcinomas.

Implications of the Study

  • The findings provide valuable insights into the EMT process in epSCC, which could help further our understanding of both the disease itself and its possible similarities with human PV-induced squamous cell carcinomas.
  • Understanding the role of papillomavirus proteins in this process could contribute to the development of new treatments or preventive strategies for this type of cancer.

Cite This Article

APA
Armando F, Mecocci S, Orlandi V, Porcellato I, Cappelli K, Mechelli L, Brachelente C, Pepe M, Gialletti R, Ghelardi A, Passeri B, Razzuoli E. (2021). Investigation of the Epithelial to Mesenchymal Transition (EMT) Process in Equine Papillomavirus-2 (EcPV-2)-Positive Penile Squamous Cell Carcinomas. Int J Mol Sci, 22(19), 10588. https://doi.org/10.3390/ijms221910588

Publication

ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 22
Issue: 19
PII: 10588

Researcher Affiliations

Armando, Federico
  • Department of Pathology, University of Veterinary Medicine Hannover, Bünteweg 17, 30559 Hannover, Germany.
Mecocci, Samanta
  • Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
Orlandi, Virginia
  • Department of Veterinary Science, University of Parma, 43121 Parma, Italy.
Porcellato, Ilaria
  • Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
Cappelli, Katia
  • Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
  • Centro di Ricerca sul Cavallo Sportivo, Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
Mechelli, Luca
  • Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
Brachelente, Chiara
  • Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
Pepe, Marco
  • Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
  • Centro di Ricerca sul Cavallo Sportivo, Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
Gialletti, Rodolfo
  • Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
  • Centro di Ricerca sul Cavallo Sportivo, Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
Ghelardi, Alessandro
  • Azienda Usl Toscana Nord-Ovest, UOC Ostetricia e Ginecologia, Ospedale Apuane, 54100 Massa, Italy.
Passeri, Benedetta
  • Department of Veterinary Science, University of Parma, 43121 Parma, Italy.
Razzuoli, Elisabetta
  • National Reference Center of Veterinary and Comparative Oncology (CEROVEC), 16129 Genova, Italy.

MeSH Terms

  • Animals
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / virology
  • Disease Models, Animal
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic
  • Horse Diseases / genetics
  • Horse Diseases / metabolism
  • Horse Diseases / virology
  • Horses / virology
  • Humans
  • Immunohistochemistry
  • Male
  • Papillomaviridae / physiology
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / virology
  • Penile Neoplasms / genetics
  • Penile Neoplasms / metabolism
  • Penile Neoplasms / virology
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Wnt Signaling Pathway / genetics
  • beta Catenin / genetics
  • beta Catenin / metabolism

Grant Funding

  • Grant IZS PLV 15/18 / Italian Ministry of Health

Conflict of Interest Statement

The authors declare no conflict of interest.

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