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Home / Equine Research Bank / Biology (Basel) / Equine Genital Squamous Cell Carcinoma Associated with EcPV2...
Biology2021; 10(3); 244; doi: 10.3390/biology10030244

Equine Genital Squamous Cell Carcinoma Associated with EcPV2 Infection: RANKL Pathway Correlated to Inflammation and Wnt Signaling Activation.

Abstract: Equine genital squamous cell carcinomas (egSCCs) are among the most common equine tumors after sarcoids, severely impairing animal health and welfare. papillomavirus type 2 (EcPV2) infection is often related to these tumors. The aim of this study was to clarify the molecular mechanisms behind egSCCs associated with EcPV2 infection, investigating receptor activator of nuclear factor-kappa B ligand (RANKL) signaling in NF-kB pathway, together with the Wnt and IL17 signaling pathways. We analyzed the innate immune response through gene expression evaluation of key cytokines and transcription factors. Moreover, Ki67 index was assessed with immunohistochemistry. EcPV2- DNA was checked, and viral presence was confirmed in 21 positive out to 23 cases (91%). Oncogene expression was confirmed in 14 cases (60.8%) for and in 8 (34.7%) for . , nuclear factor kappa-light-chain-enhancer of activated B cells ()-, , interleukin , , , , , , , , and lymphoid enhancer binding factor 1 showed a significant upregulation in tumor samples compared to healthy tissues. Our results describe an inflammatory environment characterized by the activation of RANKL/RANK and IL17 with the relative downstream pathways, and a positive modulation of inflammatory cytokines genes such as and . Moreover, the increase of , , and gene expression suggests an activation of both canonical and non-canonical Wnt signaling pathway that could be critical for carcinogenesis and tumor progression.
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Publication Date: 2021-03-21 PubMed ID: 33801021PubMed Central: PMC8003831DOI: 10.3390/biology10030244Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article explores the molecular mechanisms involved in equine genital squamous cell carcinomas (egSCCs) associated with the EcPV2 infection (papillomavirus type 2). It emphasizes on the RANKL (receptor activator of nuclear factor-kappa B ligand) signaling pathway in relation to the inflammation and Wnt signaling activation that occurs during the development of these types of carcinomas.

Research Objectives and Methodology

  • The primary goal of the study was to understand the molecular mechanisms linked to egSCCs caused by EcPV2 infection, specifically focusing on the RANKL signaling pathway, in conjunction with the Wnt and IL17 signaling pathways.
  • The researchers evaluated the innate immune response by analyzing the gene expression of significant cytokines and transcription factors.
  • In the experiment, they used immunohistochemistry to evaluate the Ki67 index, a marker of cell proliferation, and checked for the presence of EcPV2-DNA.

Findings and Observations

  • The team confirmed the presence of the EcPV2 viral DNA in 91% of the examined cases, which supports the notion that the EcPV2 infection contributes heavily to the development of egSCCs.
  • The study observed a significant upregulation in the expression of multiple genes in tumor samples when compared with healthy tissues. This includes genes involved in inflammation and the signaling pathways studied.
  • The researchers also noticed the activation of RANKL/RANK and IL17 along with their related downstream pathways. This activation was characterized by an inflammatory environment.
  • The team also found an increased expression of certain genes suggesting the activation of both the canonical (known, common) and non-canonical (lesser-known, less common) Wnt signaling pathway. This could be critically important for the onset and progression of cancerous tumors.

Implication of the Study

  • The findings of this study provide valuable insights into the mechanisms behind tumor formation in horses, specifically in relation to egSCCs. Understanding these mechanisms can aid in advancing the diagnosis, prevention, and treatment of this disease.
  • The research could also provide a foundation for further explorations into how these molecular signalling pathways are associated with other types of cancers, improving our broader understanding of carcinogenesis.

Cite This Article

APA
Mecocci S, Porcellato I, Armando F, Mechelli L, Brachelente C, Pepe M, Gialletti R, Passeri B, Modesto P, Ghelardi A, Cappelli K, Razzuoli E. (2021). Equine Genital Squamous Cell Carcinoma Associated with EcPV2 Infection: RANKL Pathway Correlated to Inflammation and Wnt Signaling Activation. Biology (Basel), 10(3), 244. https://doi.org/10.3390/biology10030244

Publication

Biology
ISSN: 2079-7737
NlmUniqueID: 101587988
Country: Switzerland
Language: English
Volume: 10
Issue: 3
PII: 244

Researcher Affiliations

Mecocci, Samanta
  • Department of Veterinary Medicine, University of Perugia, Perugia 06123, Italy.
Porcellato, Ilaria
  • Department of Veterinary Medicine, University of Perugia, Perugia 06123, Italy.
Armando, Federico
  • Department of Veterinary Science, University of Parma, Parma 43126, Italy.
  • Department of Pathology, University of Veterinary Medicine Hannover, Hannover 30559, Germany.
Mechelli, Luca
  • Department of Veterinary Medicine, University of Perugia, Perugia 06123, Italy.
Brachelente, Chiara
  • Department of Veterinary Medicine, University of Perugia, Perugia 06123, Italy.
Pepe, Marco
  • Department of Veterinary Medicine, University of Perugia, Perugia 06123, Italy.
  • Centro di Ricerca sul Cavallo Sportivo, University of Perugia, Perugia 06123, Italy.
Gialletti, Rodolfo
  • Department of Veterinary Medicine, University of Perugia, Perugia 06123, Italy.
  • Centro di Ricerca sul Cavallo Sportivo, University of Perugia, Perugia 06123, Italy.
Passeri, Benedetta
  • Department of Veterinary Science, University of Parma, Parma 43126, Italy.
Modesto, Paola
  • National Reference Center of Veterinary and Comparative Oncology (CEROVEC), Genova 16132, Italy.
Ghelardi, Alessandro
  • Azienda Usl Toscana Nord-Ovest, UOC Ostetricia e Ginecologia, Ospedale Apuane, Massa 54100, Italy.
Cappelli, Katia
  • Department of Veterinary Medicine, University of Perugia, Perugia 06123, Italy.
  • Centro di Ricerca sul Cavallo Sportivo, University of Perugia, Perugia 06123, Italy.
Razzuoli, Elisabetta
  • National Reference Center of Veterinary and Comparative Oncology (CEROVEC), Genova 16132, Italy.

Grant Funding

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

Conflict of Interest Statement

The authors declare no conflict of interest.

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Citations

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