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鉴定猫头颈鳞癌细胞中的肿瘤起始细胞及吉非替尼诱导上皮间质转化的证据。

Identification of tumour initiating cells in feline head and neck squamous cell carcinoma and evidence for gefitinib induced epithelial to mesenchymal transition.

机构信息

Royal (Dick) School of Veterinary Studies and Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK.

出版信息

Vet J. 2012 Jul;193(1):46-52. doi: 10.1016/j.tvjl.2012.01.009. Epub 2012 Feb 17.

DOI:10.1016/j.tvjl.2012.01.009
PMID:22342216
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.

摘要

猫口腔鳞状细胞癌被认为是一种高度侵袭性的癌症,具有很高的发病率。尽管进行了积极的手术,患者仍常常死于疾病,肿瘤对放射治疗和化疗具有固有敏感性。在这项研究中,我们试图鉴定具有干细胞特性的猫 SCC1 系细胞,包括内在的抵抗机制。当猫细胞处于苛刻的生长条件下时,它们形成了与干细胞表型一致的球体集落。利用 CD133,我们能够鉴定出群体中一小部分具有增强的球体形成能力、对辐射和常规化疗敏感性降低以及对 EGFR 靶向药物吉非替尼有抵抗性的细胞。此外,在吉非替尼中对猫 SSC1 细胞进行长期培养导致细胞形态和基因表达发生变化,类似于上皮到间充质转化。综上所述,这些结果表明,猫 SCC 可能是由一小部分癌症干细胞驱动的。

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