Epithelial-mesenchymal transition in an EcPV2-positive vulvar squamous cell carcinoma of a mare.
Abstract: Vulvar squamous cell carcinoma (VSCC) has been recently associated with Equus caballus papillomavirus type 2 (EcPV2) infection. Still, few reports concerning this disease are present in the literature. Objective: To describe a case of naturally occurring EcPV2-induced VSCC, by investigating tumour ability in undergoing the epithelial-to-mesenchymal transition (EMT). Methods: Case report. Methods: A 13-year-old Haflinger mare was referred for a rapidly growing vulvar mass. After surgical excision, the mass was submitted to histopathology and molecular analysis. Histopathological diagnosis was consistent with a VSCC. Real-time qPCR, real-time reverse transcriptase (RT)-qPCR and RNAscope were carried out to detect EcPV2 infection and to evaluate E6/E7 oncogenes expression. To highlight the EMT, immunohistochemistry (IHC) was performed. Expression of EMT-related and innate immunity-related genes was investigated through RT-qPCR. Results: Real-time qPCR, RT-qPCR and RNAscope confirmed EcPV2 DNA presence and expression of EcPV2 oncoproteins (E6 and E7) within the neoplastic vulvar lesion. IHC highlighted a cadherin switch together with the expression of the EMT-related transcription factor HIF1α. With RT-qPCR, significantly increased gene expression of EBI3 (45.0 ± 1.62, p < 0.01), CDH2 (2445.3 ± 0.39, p < 0.001), CXCL8 (288.7 ± 0.40, p < 0.001) and decreased gene expression of CDH1 (0.3 ± 0.57, p < 0.05), IL12A (0.04 ± 1.06, p < 0.01) and IL17 (0.2 ± 0.64, p < 0.05) were detected. Conclusions: Lack of ability to generalise and danger of over-interpretation. Conclusions: The results obtained were suggestive of an EMT event occurring within the neoplastic lesion.
© 2023 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
Publication Date: 2023-07-03 PubMed ID: 37395141DOI: 10.1111/evj.13965Google Scholar: Lookup
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Summary
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The research article describes a case of vulvar squamous cell carcinoma (VSCC) in a mare, that was induced by the Equus caballus papillomavirus type 2 (EcPV2). The team investigated the tumor’s capability for epithelial-to-mesenchymal transition (EMT) which revealed a presence of EMT event.
Case and Methodology
- The study focuses on a 13-year-old Haflinger mare that had developed a rapidly growing vulvar mass.
- The mass was surgically excised and submitted for histopathology and molecular analysis.
- Real-time qPCR, RT-qPCR, and RNAscope methods were used to detect EcPV2 presence and to evaluate expression levels of E6/E7 oncogenes.
- Immunohistochemistry (IHC) was used to highlight any signs of EMT.
- Finally, RT-qPCR also helped in studying gene expression relating to EMT and innate immunity.
Results
- The researchers were able to confirm through real-time qPCR, RT-qPCR, and RNAscope that EcPV2 DNA and the expression of EcPV2 oncoproteins (E6 and E7) were present within the neoplastic vulvar lesion.
- IHC demonstrated a cadherin switch and the expression of the EMT-related transcription factor HIF1α.
- With RT-qPCR, significant increases in gene expression of EBI3, CDH2, CXCL8, and reduced gene expression of CDH1, IL12A, and IL17 were found.
Conclusions
- The researchers warn against the danger of over-interpretation and assert the need for a cautious approach in generalizing the results.
- Nonetheless, the collected data is indicative of an EMT event occurring within the neoplastic lesion, linking the presence of EcPV2 to potential EMT events in VSCC. This suggests new directions for further research on the role of EMT in EcPV2-related cancers.
Cite This Article
APA
De Paolis L, Armando F, Montemurro V, Petrizzi L, Straticò P, Mecocci S, Guarnieri C, Pezzolato M, Fruscione F, Passeri B, Marruchella G, Razzuoli E.
(2023).
Epithelial-mesenchymal transition in an EcPV2-positive vulvar squamous cell carcinoma of a mare.
Equine Vet J.
https://doi.org/10.1111/evj.13965 Publication
Researcher Affiliations
- Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle D'Aosta, National Reference Center of Veterinary and Comparative Oncology (CEROVEC), Genova, Italy.
- Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
- Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle D'Aosta, Histopathology and Applied Technology Laboratory, Torino, Italy.
- Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.
- Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.
- Department of Veterinary Science, University of Perugia, Perugia, Italy.
- Department of Veterinary Science, University of Parma, Parma, Italy.
- Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle D'Aosta, Histopathology and Applied Technology Laboratory, Torino, Italy.
- Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle D'Aosta, National Reference Center of Veterinary and Comparative Oncology (CEROVEC), Genova, Italy.
- Department of Veterinary Science, University of Parma, Parma, Italy.
- Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.
- Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle D'Aosta, National Reference Center of Veterinary and Comparative Oncology (CEROVEC), Genova, Italy.
Grant Funding
- IZS PLV 15/18 RC / Italian Ministry of Health
- 22L03 / Region of Liguria
- 491094227 / Deutsche Forschungsgemeinschaft
- University of Veterinary Medicine Hannover Foundation
References
This article includes 39 references
- Van Den Top JGB, Ensink JM, Gröne A, Klein WR, Barneveld A, van Weeren PR. Penile and preputial tumours in the horse: literature review and proposal of a standardised approach.. Equine Vet J 2010;42(8):746-57.
- Gupta S, Kumar P, Das BC. HPV: molecular pathways and targets.. Curr Probl Cancer 2018;42(2):161-74.
- Sykora S, Brandt S. Papillomavirus infection and squamous cell carcinoma in horses.. Vet J 2017;223:48-54.
- Porcellato I, Modesto P, Cappelli K, Varello K, Peletto S, Brachelente C. Equus caballus papillomavirus type 2 (EcPV2) in co-occurring vulvar and gastric lesions of a pony.. Res Vet Sci 2020;132:167-71.
- Scase T, Brandt S, Kainzbauer C, Sykora S, Bijmholt S, Hughes K. Equus caballus papillomavirus-2 (EcPV-2): an infectious cause for equine genital cancer?. Equine Vet J 2010;42(8):738-45.
- Straticò P, Razzuoli E, Hattab J, Guerri G, Celani G, Palozzo A. Equine Gastric Squamous Cell Carcinoma in a Friesian Stallion.. J Equine Vet Sci 2022;117:104087.
- Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition.. Nat Rev Mol Cell Biol 2014;15(3):178-96.
- Micalizzi DS, Farabaugh SM, Ford HL. Epithelial-mesenchymal transition in cancer: parallels between normal development and tumor progression.. J Mammary Gland Biol Neoplasia 2010;15(2):117-34.
- Cervantes-Arias A, Pang LY, Argyle DJ. Epithelial-mesenchymal transition as a fundamental mechanism underlying the cancer phenotype.. Vet Comp Oncol 2013;11(3):169-84.
- Chang H, Liu Y, Xue M, Liu H, Du S, Zhang L. Synergistic action of master transcription factors controls epithelial-to-mesenchymal transition.. Nucleic Acids Res 2016;44(6):2514-27.
- Savagner P. The epithelial-mesenchymal transition (EMT) phenomenon.. Ann Oncol 2010;21(S7):vii89-92.
- Armando F, Mazzola F, Ferrari L, Corradi A. An overview of epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition in canine tumors: how far have we come?. Vet Sci 2022;10(1):19.
- Al Moustafa AE. E5 and E6/E7 of high-risk HPVs cooperate to enhance cancer progression through EMT initiation.. Cell Adh Migr 2015;9(5):392-3.
- Armando F, Mecocci S, Orlandi V, Porcellato I, Cappelli K, Mechelli L. Investigation of the epithelial to mesenchymal transition (EMT) process in equine papillomavirus-2 (EcPV-2)-positive penile squamous cell carcinomas.. Int J Mol Sci 2021;22(19):10588.
- Mecocci S, Porcellato I, Armando F, Mechelli L, Brachelente C, Pepe M. Equine genital squamous cell carcinoma associated with EcPV2 infection: RANKL pathway correlated to inflammation and Wnt signaling activation.. Biology 2021;10(3):244.
- Strohmayer C, Klang A, Kummer S, Walter I, Jindra C, Weissenbacher-Lang C. Tumor cell plasticity in equine papillomavirus-positive versus-negative squamous cell carcinoma of the head and neck.. Pathogens 2022;11(2):266.
- Suárez-Bonnet A, Willis C, Pittaway R, Smith K, Mair T, Priestnall SL. Molecular carcinogenesis in equine penile cancer: a potential animal model for human penile cancer.. Urol Oncol 2018;36(12):532.e9-532.e18.
- Cappelli K, Ciucis CGD, Mecocci S, Nervo T, Ines Crescio M, Pepe M. Detection of equus caballus papillomavirus type-2 in asymptomatic Italian horses.. Viruses 2022;14(8):1696.
- Porcellato I, Mecocci S, Mechelli L, Capelli K, Brachelente C, Pepe M. Equine penile squamous cell carcinomas as a model for human disease: a preliminary investigation on tumor immune microenvironment.. Cell 2020;9(11):2364.
- Armando F, Godizzi F, Razzuoli E, Leonardi F, Angelone M, Corradi A. Epithelial to mesenchymal transition (EMT) in a laryngeal squamous cell carcinoma of a horse: future perspectives.. Animals 2020;10(12):2318.
- Munday JS, Knight CG, Luff JA. Papillomaviral skin diseases of humans, dogs, cats and horses: a comparative review. Part 2: pre-neoplastic and neoplastic diseases.. Vet J 2022;288:105898.
- Yamashita-Kawanishi N, Ito S, Chambers JK, Uchida K, Sato M, Chang HW. Vulvar squamous cell carcinoma associated with Equus caballus papillomavirus type 2 infection in a Japanese mare.. Tumour Virus Res 2021;12:200226.
- Araldi RP, Sant'Ana TA, Módolo DG, de Melo GC, Spadacci-Morena DD, de Cassia Stocco R. The human papillomavirus (HPV)-related cancer biology: an overview.. Biomed Pharmacother 2018;106:1537-56.
- Barillari G, Bei R, Manzari V, Modesti A. Infection by high-risk human papillomaviruses, epithelial-to-mesenchymal transition and squamous pre-malignant or malignant lesions of the uterine cervix: a series of chained events?. Int J Mol Sci 2021;22(24):13543.
- Chen X, Bode AM, Dong Z, Cao Y. The epithelial-mesenchymal transition (EMT) is regulated by oncoviruses in cancer.. FASEB J 2016;30(9):3001-10.
- Rezaei M, Mostafaei S, Aghaei A, Hosseini N, Darabi H, Nouri M. The association between HPV gene expression, inflammatory agents and cellular genes involved in EMT in lung cancer tissue.. BMC Cancer 2020;20(1):916.
- Zhou C, Tuong ZK, Frazer IH. Papillomavirus immune evasion strategies target the infected cell and the local immune system.. Front Oncol 2019;9:682.
- Mrozik KM, Blaschuk OW, Cheong CM, Zannettino ACW, Vandyke K. N-cadherin in cancer metastasis, its emerging role in haematological malignancies and potential as a therapeutic target in cancer.. BMC Cancer 2018;18(1):939.
- Hui L, Zhang S, Dong X, Tian D, Cui Z, Qiu X. Prognostic significance of twist and N-cadherin expression in NSCLC.. PLoS One 2013;8(4):e62171.
- Tam SY, Wu VWC, Law HKW. Hypoxia-induced epithelial-mesenchymal transition in cancers: HIF-1α and beyond.. Front Oncol 2020;10:486.
- Zhang W, Shi X, Peng Y, Wu M, Zhang P, Xie R. HIF-1α promotes epithelial-mesenchymal transition and metastasis through direct regulation of ZEB1 in colorectal cancer.. PLoS One 2015;10(6):e0129603.
- Yang MH, Wu MZ, Chiou SH, Chen P-M, Chang S-Y, Liu C-J. Direct regulation of TWIST by HIF-1alpha promotes metastasis.. Nat Cell Biol 2008;10(3):295-305.
- Tang C, Liu T, Wang K, Wang X, Xu S, He D. Transcriptional regulation of FoxM1 by HIF-1α mediates hypoxia-induced EMT in prostate cancer.. Oncol Rep 2019;42(4):1307-18.
- Ma C, Guo Y, Zhang Y, Duo A, Jia Y, Liu C. PAFAH1B2 is a HIF1a target gene and promotes metastasis in pancreatic cancer.. Biochem Biophys Res Commun 2018;501(3):654-60.
- Xiong S, Dong L, Cheng L. Neutrophils in cancer carcinogenesis and metastasis.. J Hematol Oncol 2021;14(1):173.
- Ohms M, Möller S, Laskay T. An attempt to polarize human neutrophils toward N1 and N2 phenotypes in vitro.. Front Immunol 2020;11:532.
- Shaul ME, Fridlender ZG. Tumour-associated neutrophils in patients with cancer.. Nat Rev Clin Oncol 2019;16(10):601-20.
- Habiba U e, Rafiq M, Khawar MB, Nazir B, Haider G, Nazir N. The multifaceted role of IL-12 in cancer.. Adv Cancer Biol Metastasis 2022;5:100053.
- Morita Y, Masters EA, Schwarz EM, Muthukrishnan G. Interleukin-27 and its diverse effects on bacterial infections.. Front Immunol 2021;12:678515.
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