HPV related head and neck squamous cell carcinoma: New evidences for an emerging spontaneous animal model

Altamura, Gennaro; Borzacchiello, Giuseppe

doi:10.1016/j.oraloncology.2018.11.027

Cited by 6 publications

(8 citation statements)

References 7 publications

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“…FcaPV-2 was found to be the most prevalent and confirmed as the unique viral type associated with SCCF2/3 cell lines [5]. These data are in line with the growing evidence supporting a role for FcaPV-2 in development of a subset of FOSCC, such as detection of viral DNA and transcriptional activity in tumor samples and its biological similarities with mucosal HPV-16 in experimental models [4,5,26,29]; nevertheless, FcaPV-2-associated FOSCC has been proposed as a spontaneous animal model of human counterpart [1].…”

supporting

confidence: 72%

Investigation of multiple <i>Felis catus</i> papillomavirus types (-1/-2/-3/-4/-5/-6) DNAs in feline oral squamous cell carcinoma: a multicentric study

et al. 2022

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Recent evidence suggests a possible association of Felis catus papillomavirus type 2 (FcaPV-2) DNA with feline oral squamous cell carcinoma (FOSCC). In this study, type-specific PCR targeting two genes (L1/E6 or E1/E6) of FcaPV-1/-2/-3/-4/-5/-6 was performed to detect viral DNA in a large amount of FOSCC samples collected in Italy and Austria. FcaPV-1/-2/-3/-4/-5 were detected in 7/113 (6.2%), 7/93 (7.5%), 6/113 (5.3%), 1/113 (0.9%) and 2/113 (1.8%) specimens, respectively, with different prevalences in Italian vs Austrian samples, whilst FcaPV-6 went undetected. Our results confirms that FcaPV-2 is the most prevalent in FOSCC, followed by FcaPV-1/-3 and suggest that FcaPVs have variable circulation rates in European countries.

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supporting

confidence: 72%

Investigation of multiple <i>Felis catus</i> papillomavirus types (-1/-2/-3/-4/-5/-6) DNAs in feline oral squamous cell carcinoma: a multicentric study

et al. 2022

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“…7 Our study points out that FcaPV-2 infection may be an additional risk factor for the development of FOSCC as HPVs in human counterpart; moreover, FcaPV-2 E6 and E7 oncoproteins impair p53 and pRb pathways with molecular mechanisms comparable to those from mucosal HR-alpha HPVs, suggesting that FcaPV-2 induced FOSCC might be assumed as a naturally occurring animal model also for HPV-related HNSCC. 4,6,43 HR-HPVs have also been implicated as etiologic agents in nasopharyngeal cancer, thus the data obtained here in feline SCC of the nasal cavities may indicate an additional similarity with the human disease. 44 However, PV-induced human HNSCC mostly affects the oropharynx, whilst here we found FcaPV-2 in non oropharingeal sites.…”

Section: Discussionmentioning

confidence: 55%

Detection of Felis catus papillomavirus type‐2 DNA and viral gene expression suggest active infection in feline oral squamous cell carcinoma

Altamura

Cardeti

Cersini

et al. 2020

Vet Comparative Oncology

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Papillomavirus (PV) infection is associated with development of epithelial cancer in different species, including domestic cat (Felis catus). Felis catus PV type-2 (FcaPV-2) is considered the causative agent of a proportion of feline cutaneous squamous cell carcinoma (SCC), through the transforming properties of its E6 and E7 oncogenes. However, the possible role of FcaPVs in the aetiology of feline oral SCC (FOSCC) is still unclear. The aim of this study was to assess the presence and gene expression of FcaPV-2 in FOSCC samples. We detected FcaPV-2 DNA in 10/32 (31%) of the analysed FOSCC by the use of PCR methods. Importantly, viral mRNA was detected by RT-PCR in 7/10 (70%) of DNA positive samples. In particular, FcaPV-2 L1, E2 and E6E7 genes were found to be expressed in 5/10 (50%), 3/10 (33%) and 5/10 (50%) samples, respectively. Viral DNA was also detected in non neoplastic oral ulcerative lesions (ULs) (4/11, 36%); qPCR suggested a difference in viral load between ULs and FOSCCs, particularly in those expressing E6E7, although it was not statistically significant. These data suggest, but do not definively prove, a possible role of FcaPV-2 in the development of a proportion of FOSCC. Moreover, L1 and E2 gene expression results indicate that FcaPV-2 infection associated with these tumours may possibly be productive.

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“…The similarities between human and pet tumors lay the foundations of “comparative oncology,” with the dual aim of developing therapies in humans based on the studies in spontaneous animal models and/or translating the therapies used in humans into veterinary medicine ( 5 ). At this regard, FOSCC shares several biological properties with HNSCC such as over-expression of EGFR ( 10 ) and, in a subset of tumors, association with PV infection, mainly by Felis catus PV type 2 (FcaPV-2), thus it is considered a reliable spontaneous animal model of human counterpart ( 11 – 13 ). Furthermore, several studies suggest that expression of EGFR is a marker of poor prognosis also in FOSCC ( 10 , 14 , 15 ) and, accordingly, that EGFR plays a key role in tumor cells proliferation and survival, suggesting that it may be a promising molecular target in this feline cancer as well ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

Anti-EGFR monoclonal antibody Cetuximab displays potential anti-cancer activities in feline oral squamous cell carcinoma cell lines

Altamura

Borzacchiello

2022

Front. Vet. Sci.

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Feline oral squamous cell carcinoma (FOSCC) is a malignant tumor characterized by an aggressive behavior and poor prognosis, for which no fully effective therapies are available. Studies of comparative oncology suggest that epidermal growth factor receptor (EGFR) may be a therapeutic target in FOSCC, similarly to human head and neck SCC (HNSCC), where the use of anti-EGFR monoclonal antibody Cetuximab has entered the clinical practice. The aim of this study was to assess the efficacy of Cetuximab in three validated preclinical models of FOSCC (SCCF1, SCCF2, SCCF3). Sequencing of tyrosine kinase domain of EGFR in the cell lines revealed a wild-type genotype, excluding the presence of activating mutations. Western blotting experiments demonstrated that Cetuximab inhibited activation of EGFR and its downstream kinase Akt in SCCF1, SCCF2 and SCCF3 along with HNSCC cell line CAL 27 included as control. Importantly, CCK-8 and trypan blue exclusion assays revealed that treatment with Cetuximab caused a decrease in cell proliferation and cell viability in all cell lines, with a general dose- and time-dependent trend. Cell death induced by Cetuximab was associated with cleavage of PARP, indicating occurrence of apoptosis. Taken together, our data suggest that Cetuximab exerts potential anti-cancer activities in FOSCC, paving the way for future translational studies aimed at assessing its employment in the therapy of this lethal cancer of cats.

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HPV related head and neck squamous cell carcinoma: New evidences for an emerging spontaneous animal model

Cited by 6 publications

References 7 publications

Investigation of multiple <i>Felis catus</i> papillomavirus types (-1/-2/-3/-4/-5/-6) DNAs in feline oral squamous cell carcinoma: a multicentric study

Investigation of multiple <i>Felis catus</i> papillomavirus types (-1/-2/-3/-4/-5/-6) DNAs in feline oral squamous cell carcinoma: a multicentric study

Detection of Felis catus papillomavirus type‐2 DNA and viral gene expression suggest active infection in feline oral squamous cell carcinoma

Anti-EGFR monoclonal antibody Cetuximab displays potential anti-cancer activities in feline oral squamous cell carcinoma cell lines

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