[show abstract][hide abstract] ABSTRACT: Feline oral squamous cell carcinoma is considered a highly invasive cancer that carries a high level of morbidity. Despite aggressive surgery, patients often succumb to disease, the tumour having inherent insensitivity to radiation and chemotherapy. In this study we sought to identify cells within the feline SCC1 line that have stem cell properties, including inherent resistance mechanisms. When feline cells were subjected to harsh growth conditions, they formed sphere colonies consistent with a stem cell phenotype. Utilising CD133, we were able to identify a small fraction of cells within the population that had enhanced sphere-forming ability, reduced sensitivity to radiation and conventional chemotherapy and demonstrated resistance to the EGFR-targeting drug, gefitinib. In addition, long-term culture of feline SSC1 cells in gefitinib caused a change in cell morphology and gene expression reminiscent of an epithelial to mesenchymal transition. Taken together, these results suggest that feline SCC may be driven by small subset of cancer stem cells.
The Veterinary Journal 02/2012; 193(1):46-52. · 2.42 Impact Factor
[show abstract][hide abstract] ABSTRACT: The cancer stem cell (CSC) hypothesis proposes that tumour growth is maintained by a distinct subpopulation of 'CSC'. This study applied flow cytometric methods, reported to detect CSC in both primary and cultured cancer cells of other species, to identify candidate canine subpopulations. Cell lines representing diverse canine malignancies, and cells derived from spontaneous canine tumours, were evaluated for expression of stem cell-associated surface markers (CD34, CD44, CD117 and CD133) and functional properties [Hoecsht 33342 efflux, aldehyde dehydrogenase (ALDH) activity]. No discrete marker-defined subsets were identified within established cell lines; cells derived directly from spontaneous tumours demonstrated more heterogeneity, although this diminished upon in vitro culture. Functional assays produced variable results, suggesting context-dependency. Flow cytometric methods may be adopted to identify putative canine CSC. Whilst cell lines are valuable in assay development, primary cells may provide a more rewarding model for studying tumour heterogeneity in the context of CSC. However, it will be essential to fully characterize any candidate subpopulations to ensure that they meet CSC criteria.
Veterinary and Comparative Oncology 10/2011; · 1.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: Health-related quality-of-life (HRQoL) has been studied extensively in human medicine. There is currently no standard HRQoL evaluation for veterinary oncology patients. The aim of this study was to assess the practicality, usefulness and robustness, from a pet owner and clinician perspective, of a questionnaire for the assessment of HRQoL in canine and feline cancer patients. A HRQoL assessment entitled 'Cancer Treatment Form' and two questionnaires entitled 'Owner Minitest' and 'Clinician Minitest' were designed. The first and second were completed by owners of patients presenting to a veterinary oncology referral service and the third by attending clinicians. The 'Cancer Treatment Form' was well received by owners and clinicians and provided a valuable assessment of HRQoL with 98% (82/84) of owners reporting an accurate reflection of their pet's quality-of-life. Following this, minor improvements to the form could be suggested prior to regular use in evaluation of clinical oncology patients.
Veterinary and Comparative Oncology 09/2011; 9(3):172-82. · 1.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aims of this study were to establish expression of epidermal growth factor receptor (EGFR) and Ki67 in 67 archived biopsy samples of feline oral squamous cell carcinomas (FOSCCs) and to establish if the expression of either markers was predictive of survival. Samples were immunohistochemically labelled for the two proteins and scored. Statistical analyses of data, including Kaplan-Meier survival curves, were performed. All samples expressed both markers although levels differed between samples. Median overall survival was 46 days and 1-year survival was 5%. There was no correlation between Ki67 and EGFR scores (Pearson's correlation coefficient, P = 0.861). Low cellular proliferation (low Ki67 score) was positively correlated with an overall longer survival (Log Rank, P = 0.02) and a trend towards better survival for the high EGFR group was observed (Log Rank, P = 0.076). Ki67 and EGFR immunostaining in FOSCC may be of value as biochemical markers for screening of biopsies from cases of FOSCC.
Veterinary and Comparative Oncology 06/2011; 9(2):106-17. · 1.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: The cancer stem cell hypothesis proposes that tumours are maintained by a population of cancer stem cells (CSC), which must be eradicated to prevent disease relapse after treatment. Cells expressing high levels of CD44 have been identified as candidate CSC in a variety of human tumours. This study sought to investigate CD44 expression and its potential as a CSC marker in canine cancer.
CD44 expression in several canine cancer cell lines was determined by flow cytometry. Cells with low and high levels of CD44 expression were examined for differences in growth characteristics, colony forming ability, drug sensitivity and cell cycle profile.
CD44(High) cells demonstrated enhanced growth and colony forming capacity, under both adherent and low-density serum free ("tumoursphere") conditions. However, no difference in sensitivity to doxorubicin was seen between the two populations. Moreover, whilst most CD44(Low) cells were in resting or G₁ growth phase, an increased proportion of CD44(High) cells were in G₂M phase of the cell cycle. Upon proliferation in culture, both populations gave rise to progeny with a full spectrum of CD44 expression.
CD44 expression is associated with proliferation in cultured canine cancer cells, but transient and fluctuating expression may limit its utility as a CSC marker.
Veterinary Immunology and Immunopathology 02/2011; 141(1-2):46-57. · 1.88 Impact Factor
[show abstract][hide abstract] ABSTRACT: Interferons (IFNs) are naturally produced cytokines with multiple important biological functions. The activity of recombinant feline IFN-omega (rFeIFN-omega) alone and in combination with chemotherapeutic drugs was tested on canine and feline mammary carcinoma cell lines (REM134 and CAT-MT) and putative tumour-initiating cells (TIC) derived from these cell lines by sphere assay. Viability was measured by chemoluminescence and a one-way analysis of variance and Student's t-tests were used for statistical analysis. rFeIFN-omega showed in vitro antitumour activity on feline and canine mammary carcinoma cells and putative TICs with a dose-dependent and target cell-specific action. Putative TICs were more resistant to the action of rFeIFN-omega compared with daughter REM134 and CAT-MT cells. REM134 cells and TICs were more sensitive to rFeIFN-omega compared with the feline counterparts. An additive effect was noticed between rFeIFN-omega and conventional anticancer drugs, in particular following co-culture of cells with anthracycline drugs. The results suggest that rFeIFN-omega warrants further investigation as a therapeutic adjunct in feline and canine mammary tumours.
Veterinary and Comparative Oncology 12/2009; 7(4):222-9. · 1.56 Impact Factor