Investigation of multiple Felis catus papillomavirus types (-1/-2/-3/-4/-5/-6) DNAs in feline oral squamous cell carcinoma: a multicentric study.
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ABSTRACT:
SUBMITTER: Altamura G
PROVIDER: S-EPMC9246691 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Findings from polymerase chain reaction-based methods have suggested a role of Felis catus papillomavirus 2 (FcaPV-2) in the development of feline cutaneous squamous cell carcinoma (SCC). However, because polymerase chain reaction cannot localize deoxyribonucleic acid or ribonucleic acid within the lesion, it is difficult to differentiate a coincidental FcaPV-2 infection and a causative association. Given that a key event in the pathogenesis of human papillomavirus-induced cancer is the expression of viral E6 and E7 oncogenes, localization of FcaPV-2 E6 and E7 transcription within neoplastic cells in feline SCCs would support a causative role for this papillomavirus. Therefore, RNAscope in situ hybridization was used to localize FcaPV-2 E6 and E7 transcripts in 18 formalin-fixed paraffin-embedded samples of cutaneous SCC. Positive signals were present within 5 of 9 samples (56%) from ultraviolet-protected sites and 0 of 9 samples from ultraviolet-exposed sites. In the 4 in situ hybridization-positive samples that contained adjacent hyperplastic skin, hybridization patterns in these regions were characterized by intense nuclear signals within the superficial epidermis and punctate signals within the basal epithelial layers. However, within the 5 SCCs, punctate signals were present within all layers of the epidermis, with progressive loss of intense nuclear signals within the superficial epidermis. This hybridization pattern is consistent with unregulated E6 and E7 transcription and decreased viral replication and is similar to the pattern observed in human papillomavirus-induced cancers as they progress from hyperplastic lesions containing productive infections to nonproductive neoplasms. These findings support a causative role for FcaPV-2 in the pathogenesis of feline SCC.
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Project description:A 12-year-old neutered male domestic shorthair cat was presented with a 3-year history of multiple nonpruritic, ulcerated, plaque-like skin lesions but no other clinical signs. A systemic examination revealed mild lymphadenopathy. Histopathologic analysis of the skin lesions revealed multicentric basosquamous carcinoma (BSC). Immunohistochemical analysis, PCR, and sequencing detected Felis catus papillomavirus type 2 (FcaPV-2) within the tumors. As BSC is rare in cats, clinical behavior has not been established. To our knowledge, this is the first case report to demonstrate detection of FcaPV-2 within a BSC in a domestic cat.
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Project description:Telomerase activity contributes to cell immortalization by avoiding telomere shortening at each cell division; indeed, its catalytic subunit telomerase reverse transcriptase (TERT) is overexpressed in many tumors, including human oral squamous cell carcinoma (hOSCC). In these tumors, matrix metalloproteinases (MMPs), a group of zinc-dependent endopeptidases involved in cell migration, contribute to invasive potential of cancer cells. A proportion of hOSCC is associated with infection by high-risk human papillomavirus (HR-HPVs), whose E6 oncogene enhances TERT and MMPs expression, thus promoting cancer progression. Feline oral squamous cell carcinoma (FOSCC) is a malignant tumor with highly invasive phenotype; however, studies on telomerase activity, TERT, and MMPs expression are scarce. In this study, we demonstrate telomerase activity, expression of TERT, and its transcriptional activator cMyc along with expression of MMP-1, -2, and -9 in FOSCC-derived cell lines SCCF2 and SCCF3, suggesting a contribution by these pathways in cell immortalization and invasion in these tumors. Recent studies suggest that a sub-group of FOSCC as well as SCCF2 and SCCF3 are associated with Felis catus PV type-2 (FcaPV-2) infection. However, in this work, FcaPV-2 E6 gene knock-down caused no shift in either TERT, cMyc, or MMPs levels, suggesting that, unlike its human counterpart, the viral oncogene plays no role in their regulation.
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Project description:The idea of animals possessing personalities was once dismissed by the scientific community, but has since gained traction with evidence for potential application to improve captive animal management and welfare. Although domestic cats are popular companion animals, research has tended to overlook the value of personality assessment for management and care of pet cats. The aim of this study was to investigate personality in a large sample of pet cats with a view to understanding practical implications for pet cats in the home. Personality of 2,802 pet cats, from South Australia and New Zealand, was rated by their owners utilising a survey measuring 52 personality traits. Five reliable personality factors were found using principal axis factor analysis: Neuroticism, Extraversion, Dominance, Impulsiveness and Agreeableness. Implications for the 'Feline Five' are discussed in relation to their potential application to improving the management and welfare of pet cats. Highly Impulsive cats for example, may be reacting to something stressful in their environment, whereas cats with low Agreeableness scores, showing irritability may indicate underlying pain or illness. Thus, the need for a systematic and holistic approach to personality that includes both the individual pet cat and its environment is recommended, and opens the door to future interdisciplinary intervention.
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Project description:Studying the evolutionary mechanisms of feline immunodeficiency virus in the domestic cat (Felis catus), FIV(Fca), provides a good comparison to other lentiviruses, such as HIV and FIV(Pco) in the cougar (Puma concolor). We review the current epidemiological and evolutionary findings of FIV(Fca). In addition to the five accepted FIV(Fca), subtypes, several recent phylogenetic studies have found strains that form separate clades, indicative of novel subtypes. In New Zealand cats, these strains of unknown subtype have been found to be involved in complex patterns of intergenic recombination, and whole genome sequences are required to resolve these. Evidence of recombination events has been documented with the highest levels in the env gene, the region involved in host cell receptor recognition. Several cases of FIV(Fca) multiple infections, both inter- and intra-subtype, have been reported. The findings of both unknown subtypes and relatively high levels of recombination suggest the need for further testing of the current vaccine. Limited studies on the evolutionary rate of FIV(Fca) document a value twice to three times that of FIV in the cougar, a result suggesting the different levels of co-adaptation between the viruses and their respective hosts. We studied the tissue distribution of FIV(Fca) in feral domestic cats, finding the first case of FIV compartmentalisation, a phenomenon well documented in HIV-1 patients.
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Project description:Association of felis catus papillomaviruses (FcaPVs) with feline squamous cell carcinoma (SCC) has been reported worldwide, while there is limited information about FcaPVs in Asia. In this study, 21 feline SCC biopsy samples from cats in Japan were analyzed by PCR with PV consensus primers and type-specific primers for FcaPV type 2 (FcaPV-2), FcaPV-3 and FcaPV-4 designed in this study. Sequence analysis revealed that one sample was FcaPV-3, and two were FcaPV-4. In both FcaPV-4 positive samples, 334th tryptophan in L1 ORF was deleted compared with the reference sequence. Moreover, immunohistochemistry showed that p16 protein was positive in both FcaPV-4 detected samples. This study would contribute to the molecular epidemiological and pathological understanding of FcaPV in Japan.
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Project description:Felis catus papillomavirus (FcaPV), especially type 2 (FcaPV2) is considered as one of the causative agents in squamous cell carcinoma (SCC) in cats. However, our previous study detected FcaPV3 and FcaPV4, but not FcaPV2 in feline SCCs collected in Japan, suggesting that the prevalence of FcaPV2 in SCC may vary depending on geographic locations. To evaluate this hypothesis, two conventional PCR reactions targeting E1 and E7 genes were performed to detect FcaPV2 in feline SCC samples collected in Taiwan and Japan. While 46.9% (23/49) of feline SCC cases from Taiwan were PCR positive for FcaPV2, only 8.6% (3/35) cases from Japan were positive. Our result suggests that the prevalence of FcaPV2 in feline SCCs may depend on the region.
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Project description:Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine tumor, and more than 90% of feline MCC cases test positive for Felis catus papillomavirus type 2 (FcaPV2). In the present study, basal cell markers p40, p63, and p73 and the stem cell marker SOX2 and cytokeratin 14 (CK14) were immunohistochemically examined in normal fetal, infant, and adult feline skin tissues. The expression of these proteins was examined in tumors positive for FcaPV2, including MCC, basal cell carcinoma (BCC), Bowenoid in situ carcinoma (BISC), and squamous cell carcinoma (SCC). Infant and adult feline skin tissues had mature Merkel cells, which were CK14-, CK18+, CK20+, SOX2+, synaptophysin+ and CD56+, while fetal skin tissue had no mature Merkel cells. MCC was immunopositive for p73, CK18, and SOX2 in 32/32 cases, and immunonegative for CK14 in 31/32 cases and for p40 and p63 in 32/32 cases. These results indicate that MCC exhibits different immunophenotypes from Merkel cells (p73-) and basal cells (p40+, p63+, and SOX2-). In contrast, all 3 BCCs, 1 BISC, and 2 SCCs were immunopositive for the basal cell markers p40, p63, and p73. The life cycle of papillomavirus is closely associated with the differentiation of infected basal cells, which requires the transcription factor p63. Changes in p63 expression in FcaPV2-positive MCC may be associated with unique cytokeratin expression patterns (CK14-, CK18+, and CK20+). Furthermore, SOX2 appears to be involved in Merkel cell differentiation in cats, similar to humans and mice.
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Project description:Feline oral squamous cell carcinomas (FOSCC) are highly aggressive neoplasms with short survival times despite multimodal treatment. FOSCC are similar to squamous cell carcinomas of the head and neck (SCCHN) in humans, which also present therapeutic challenges. The current study was undertaken to identify novel chemotherapeutics using FOSCC cell lines. A high throughput drug screen using 1,952 drugs was performed to identify chemotherapeutics for further investigation. Two of the drugs identified in the drug screen, actinomycin D and methotrexate, and two drugs with similar molecular targets to drugs found to be efficacious in the screening, dinaciclib and flavopiridol, were selected for further investigation. Drug inhibition profiles were generated for each drug and cell line using an MTS assay. In addition, the effects of the drugs of interest on cell cycle progression were analyzed via a propidium iodide DNA labeling assay. Changes in caspase-3/7 activity after treatment with each drug were also determined. The findings demonstrated effectiveness of the drugs at nanomolar concentrations with sensitivity varying across cell lines. With all of the drugs except for actinomycin D, evidence for G1 arrest was found. Dinaciclib and flavopiridol were demonstrated to induce apoptosis. The results of the study suggest that the selected drugs are potential candidates for developing novel chemotherapeutic approaches to FOSCC. Through these studies, novel therapeutic strategies for the treatment of FOSCC can be developed to provide better care for affected cats which can also serve as proof of concept studies to inform translational studies in SCCHN in humans.
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Project description:There has been little research into brachycephalism and associated disorders in cats. A questionnaire aimed at cat owners was used to determine the relationship between feline facial conformation and owner-reported cat management requirements and respiratory abnormalities. Owner-submitted photographs of cats were used to develop novel measures of skull conformation. One thousand valid questionnaires were received. Within these there were 373 valid photographs that allowed measurement of muzzle ratio (M%) and 494 that allowed nose position ratio (NP%). The data included 239 cats for which both measurements were available. Owners reported lifestyle factors (e.g. feeding type, grooming routine, activity level), physical characteristics (e.g. hair length) and other health characteristics of their cat (e.g. tear staining, body condition score). A composite respiratory score (RS) was calculated for each cat using their owner's assessment of respiratory noise whilst their cat was asleep and then breathing difficulty following activity. Multivariate analyses were carried out using linear models to explore the relationship between RS and facial conformation, and lifestyle risk factors. The results showed that reductions in NP% and M% were significantly associated with RS (P < 0.001 and P = 0.026, respectively) and that the relationship was significantly negatively correlated (r = -0.56, P < 0.001 for both). Respiratory score was also significantly associated with increased presence of tear staining (P < 0.001) and a sedentary lifestyle (P = 0.01). This study improves current knowledge concerning cats with breeding-related alterations in skull confirmation and indicates that brachycephalism may have negative respiratory implications for cat health and welfare, as has been previously shown in dogs.
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