Combined zoledronic acid and meloxicam reduced bone loss and tumour growth in an orthotopic mouse model of bone‐invasive oral squamous cell carcinoma

Martin, Chelsea K.; Dirksen, Wessel P.; Carlton, Michelle M.; Lanigan, Lisa G.; Pillai, Smitha P.S.; Werbeck, Jillian L.; Simmons, Jessica K.; Hildreth, Blake E.; London, Cheryl A.; Toribio, Ramiro E.; Rosol, Thomas J.

doi:10.1111/vco.12037

Cited by 18 publications

(13 citation statements)

References 52 publications

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“…Feline oral SCC (either in clinical patients, cell lines or immunohistochemical studies) has been used as a model for tumor hypoxia (which may be targeted to improve responses to chemo- or radio-therapy) [ 57 ] and mechanisms and treatment of bone invasion [ 51 , 58 , 59 , 60 , 61 ]. EGFR is a druggable target in HHNC [ 42 ], and the feline and human EGFR sequences are highly homologous [ 10 ].…”

Section: Feline Oral Squamous Cell Carcinomamentioning

confidence: 99%

Cats, Cancer and Comparative Oncology

Cannon

2015

Veterinary Sciences

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Naturally occurring tumors in dogs are well-established models for several human cancers. Domestic cats share many of the benefits of dogs as a model (spontaneous cancers developing in an immunocompetent animal sharing the same environment as humans, shorter lifespan allowing more rapid trial completion and data collection, lack of standard of care for many cancers allowing evaluation of therapies in treatment-naïve populations), but have not been utilized to the same degree in the One Medicine approach to cancer. There are both challenges and opportunities in feline compared to canine models. This review will discuss three specific tumor types where cats may offer insights into human cancers. Feline oral squamous cell carcinoma is common, shares both clinical and molecular features with human head and neck cancer and is an attractive model for evaluating new therapies. Feline mammary tumors are usually malignant and aggressive, with the ‘triple-negative’ phenotype being more common than in humans, offering an enriched population in which to examine potential targets and treatments. Finally, although there is not an exact corollary in humans, feline injection site sarcoma may be a model for inflammation-driven tumorigenesis, offering opportunities for studying variations in individual susceptibility as well as preventative and therapeutic strategies.

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Section: Feline Oral Squamous Cell Carcinomamentioning

confidence: 99%

Cats, Cancer and Comparative Oncology

Cannon

2015

Veterinary Sciences

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“…For example, COX-2 has been shown to be expressed in a subset of feline OSCC biopsies [ 16 ]. Additionally, feline OSCC cell lines express COX-2 and STAT3 (a transcription factor important in inflammation and tumor progression), and have demonstrated sensitivity to COX inhibitors [ 17 , 18 , 19 ]. Although anti-inflammatory therapy has shown promise for the treatment of animal cancer, there are risks of gastric and renal toxicity; these drugs must be used with caution [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

CD147 and Cyclooxygenase Expression in Feline Oral Squamous Cell Carcinoma

Nasry

Wang

Jones

et al. 2018

Veterinary Sciences

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Feline oral squamous cell carcinoma (OSCC) is a highly invasive form of cancer in cats. In human OSCC, cluster of differentiation 147 (CD147) contributes to inflammation and tumor invasiveness. CD147 is a potential therapeutic target, but the expression of CD147 in feline OSCC has not been examined. Immunohistochemistry was used to determine if cyclooxygenase 2 (COX-2) and CD147 expression in feline OSCC biopsies was coordinated. Tumor cells were more likely to express COX-2 (22/43 cases or 51%) compared to stroma (8/43 or 19%) and adjacent oral epithelium (9/31 cases or 29%) (p < 0.05). CD147 was also more likely to occur in tumor cells compared to stroma and adjacent mucosa, with 21/43 (49%) of cases having >50% tumor cells with mild or moderate CD147 expression, compared to 9/28 (32%) in adjacent epithelium and only 5/43 (12%) in adjacent stroma (p < 0.05). In feline OSCC cell lines (SCCF1, SCCF2, and SCCF3), CD147 gene expression was more consistently expressed compared to COX-2, which was 60-fold higher in SCCF2 cells compared to SCCF1 cells (p < 0.05). CD147 expression did not correlate with COX-2 expression and prostaglandin E2 (PGE2) secretion, indicating that they may be independently regulated. CD147 potentially represents a novel therapeutic target for the treatment of feline OSCC and further study of CD147 is warranted.

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“…Importantly, our studies revealed COX-2 expression in both tumor epithelium and stroma with positive stroma cells identified as fibroblasts based on morphology. COX-2 expression within the stroma of feline OSCC has not been previously described, although a more recent study described COX-2 expression in all feline OSCC cell lines including a cell line derived from tumor associated fibroblasts (Martin et al, 2015). Examination of larger patient cohorts and further investigation of cell types expressing COX-2 will be necessary to determine the role of this immune mediator as a prognostic factor and therapeutic target for feline OSCC.…”

Section: Discussionmentioning

confidence: 99%

Investigation of immune cell markers in feline oral squamous cell carcinoma

Sparger

Murphy

Kamal

et al. 2018

Veterinary Immunology and Immunopathology

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Squamous cell carcinoma is the most common oral cancer in the cat and presents as a locally aggressive lesion for which an effective therapeutic protocol remains elusive. Feline oral squamous cell carcinoma (OSCC) shares many clinical characteristics with human head and neck squamous cell carcinoma (HNSCC). Accordingly, present studies were conducted to determine similarities for immune markers shared by feline OSCC and human HNSCC. Biopsies harvested from a feline patient cohort-1 (n = 12) were analyzed for lymphoid cell infiltrates by immunohistochemistry (IHC). Results revealed unique patterns of T cell infiltration involving both neoplastic epithelium and stroma that were detected in most patient tumor biopsies (92%) examined by IHC staining for CD3. Intratumoral B cell infiltrates were detected within tumor stroma only, based on IHC staining for CD79a and CD20 for all patients within the same cohort-1. Infiltration of tumors by a regulatory CD4 T cell subset (Tregs) defined by expression of the forkhead transcription factor FoxP3, was also detected in biopsies from 57% of patients and involved infiltration of neoplastic epithelium and stroma. Patient biopsies were also examined for expression of immunomodulator cyclooxygenase (COX)-2 and revealed positive but weak staining of neoplastic epithelium in a significant proportion of cases (75%). Interestingly, COX-2 expression was detected in both neoplastic epithelium and stroma. Blood collected from a second cohort of feline OSCC patients (n = 9) revealed an increased frequency of circulating CD4+FoxP3+ T cells when compared to healthy adult controls (n = 7) (P = 0.045), although frequencies of CD4+CD25+FoxP3+ T cells were comparable between patients and healthy pet cat controls. Lastly, biopsies from feline OSCC patients were characterized for histologic subtype using a classification scheme previously described for human HNSCC. This analysis revealed the conventional subtype as the predominant variant (75%) with conventional subtypes split evenly between well differentiated and moderately differentiated carcinomas. Two cases were classified as papillary and one case as basaloid subtypes. Correlations between subtype, immune marker scores or circulating Treg frequencies and clinical characteristics or outcome were not detected, most likely due to small patient numbers within patient cohorts. However, findings from these studies provide a preliminary step in the characterization of immune and histologic markers that will be critical to defining prognostic immune markers for feline OSCC and potential targets for testing of immunotherapeutics also relevant to human HNSCC in future studies.

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Combined zoledronic acid and meloxicam reduced bone loss and tumour growth in an orthotopic mouse model of bone‐invasive oral squamous cell carcinoma

Cited by 18 publications

References 52 publications

Cats, Cancer and Comparative Oncology

Cats, Cancer and Comparative Oncology

CD147 and Cyclooxygenase Expression in Feline Oral Squamous Cell Carcinoma

Investigation of immune cell markers in feline oral squamous cell carcinoma

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