title: Identification of tumour initiating cells in feline head and neck squamous cell carcinoma and evidence for gefitinib induced epithelial to mesenchymal transition.
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.
authors.affiliation: Royal (Dick) School of Veterinary Studies and Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK. Lisa.pang@ed.ac.uk
authors.forename: L Y
authors.initials: LY
authors.lastname: Pang
authors.forename: G T
authors.initials: GT
authors.lastname: Bergkvist
authors.forename: A
authors.initials: A
authors.lastname: Cervantes-Arias
authors.forename: D A
authors.initials: DA
authors.lastname: Yool
authors.forename: R
authors.initials: R
authors.lastname: Muirhead
authors.forename: D J
authors.initials: DJ
authors.lastname: Argyle
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D002371:Cat Diseases / Q000188:drug therapy* / Q000532:radiotherapy*; D002415:Cats; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000077156:Gefitinib; D006023:Glycoproteins / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D010455:Peptides / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000970:Antineoplastic Agents; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib