PMID- 33801021
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210413
IS  - 2079-7737 (Print)
IS  - 2079-7737 (Electronic)
IS  - 2079-7737 (Linking)
VI  - 10
IP  - 3
DP  - 2021 Mar 21
TI  - Equine Genital Squamous Cell Carcinoma Associated with EcPV2 Infection: RANKL 
      Pathway Correlated to Inflammation and Wnt Signaling Activation.
LID - 10.3390/biology10030244 [doi]
LID - 244
AB  - Equine genital squamous cell carcinomas (egSCCs) are among the most common equine 
      tumors after sarcoids, severely impairing animal health and welfare. Equus 
      caballus 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-E6 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 E6 and in 8 (34.7%) for 
      E2. RANKL, nuclear factor kappa-light-chain-enhancer of activated B cells 
      (NFKB)-p50, NFKBp65, interleukin (IL)-6, IL17, IL23p19, IL8, IL12p35, IL12p40, 
      beta-catenin (BCATN1), FOS like 1 (FOSL1), and lymphoid enhancer binding factor 1 
      (LEF1) 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 IL6 and IL8. 
      Moreover, the increase of BCATN1, FOSL1, and LEF1 gene expression suggests an 
      activation of both canonical and non-canonical Wnt signaling pathway that could 
      be critical for carcinogenesis and tumor progression.
FAU - Mecocci, Samanta
AU  - Mecocci S
AUID- ORCID: 0000-0003-2998-0412
AD  - Department of Veterinary Medicine, University of Perugia, Perugia 06123, Italy.
FAU - Porcellato, Ilaria
AU  - Porcellato I
AUID- ORCID: 0000-0003-2882-6739
AD  - Department of Veterinary Medicine, University of Perugia, Perugia 06123, Italy.
FAU - Armando, Federico
AU  - Armando F
AUID- ORCID: 0000-0002-2578-4409
AD  - Department of Veterinary Science, University of Parma, Parma 43126, Italy.
AD  - Department of Pathology, University of Veterinary Medicine Hannover, Hannover 
      30559, Germany.
FAU - Mechelli, Luca
AU  - Mechelli L
AD  - Department of Veterinary Medicine, University of Perugia, Perugia 06123, Italy.
FAU - Brachelente, Chiara
AU  - Brachelente C
AUID- ORCID: 0000-0002-4812-3216
AD  - Department of Veterinary Medicine, University of Perugia, Perugia 06123, Italy.
FAU - Pepe, Marco
AU  - Pepe M
AD  - Department of Veterinary Medicine, University of Perugia, Perugia 06123, Italy.
AD  - Centro di Ricerca sul Cavallo Sportivo, University of Perugia, Perugia 06123, 
      Italy.
FAU - Gialletti, Rodolfo
AU  - Gialletti R
AD  - Department of Veterinary Medicine, University of Perugia, Perugia 06123, Italy.
AD  - Centro di Ricerca sul Cavallo Sportivo, University of Perugia, Perugia 06123, 
      Italy.
FAU - Passeri, Benedetta
AU  - Passeri B
AUID- ORCID: 0000-0003-4660-3336
AD  - Department of Veterinary Science, University of Parma, Parma 43126, Italy.
FAU - Modesto, Paola
AU  - Modesto P
AUID- ORCID: 0000-0002-8865-2366
AD  - National Reference Center of Veterinary and Comparative Oncology (CEROVEC), 
      Genova 16132, Italy.
FAU - Ghelardi, Alessandro
AU  - Ghelardi A
AUID- ORCID: 0000-0002-3686-1481
AD  - Azienda Usl Toscana Nord-Ovest, UOC Ostetricia e Ginecologia, Ospedale Apuane, 
      Massa 54100, Italy.
FAU - Cappelli, Katia
AU  - Cappelli K
AUID- ORCID: 0000-0002-3141-771X
AD  - Department of Veterinary Medicine, University of Perugia, Perugia 06123, Italy.
AD  - Centro di Ricerca sul Cavallo Sportivo, University of Perugia, Perugia 06123, 
      Italy.
FAU - Razzuoli, Elisabetta
AU  - Razzuoli E
AUID- ORCID: 0000-0002-6597-475X
AD  - National Reference Center of Veterinary and Comparative Oncology (CEROVEC), 
      Genova 16132, Italy.
LA  - eng
GR  - IZS PLV 15/18 RC/Italian Ministry of Health/
PT  - Journal Article
DEP - 20210321
PL  - Switzerland
TA  - Biology (Basel)
JT  - Biology
JID - 101587988
PMC - PMC8003831
OTO - NOTNLM
OT  - E6 expression
OT  - EcPV2
OT  - IL12
OT  - IL17A
OT  - IL23
OT  - RANKL pathway
OT  - Wnt pathway
OT  - equine
OT  - inflammation
COIS- The authors declare no conflict of interest.
EDAT- 2021/04/04 06:00
MHDA- 2021/04/04 06:01
PMCR- 2021/03/21
CRDT- 2021/04/03 01:07
PHST- 2021/02/20 00:00 [received]
PHST- 2021/03/16 00:00 [revised]
PHST- 2021/03/17 00:00 [accepted]
PHST- 2021/04/03 01:07 [entrez]
PHST- 2021/04/04 06:00 [pubmed]
PHST- 2021/04/04 06:01 [medline]
PHST- 2021/03/21 00:00 [pmc-release]
AID - biology10030244 [pii]
AID - biology-10-00244 [pii]
AID - 10.3390/biology10030244 [doi]
PST - epublish
SO  - Biology (Basel). 2021 Mar 21;10(3):244. doi: 10.3390/biology10030244.