García-Marín Rocío, Cabal Virginia N, Fernández-Cedrón Bermejo Carmen, Riobello Cristina, Suárez-Fernández Laura, Codina-Martínez Helena, Navarro-García Ainhoa, Lorenzo-Guerra Sara Lucila, García-Martínez Jorge, Vivanco Blanca, López Fernando, Llorente José Luis, Hermsen Mario A
Department of Head and Neck Cancer, Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain.
Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain.
Otolaryngol Head Neck Surg. 2023 Apr;168(4):729-737. doi: 10.1177/01945998221089186. Epub 2023 Feb 5.
To characterize cell line CAE606 derived from a squamous cell carcinoma (SCC) of the external auditory canal (EAC) and to show its usefulness as a model for testing candidate therapeutic agents.
Preclinical translational research.
Biomedical research institute.
The cell line was initiated from a moderately differentiated T2N0M0 EAC SCC. We studied its histologic and genetic features as well as growth and invasion parameters. Sensitivity to cell CDK4/6 cell cycle inhibitor palbociclib was analyzed.
CAE606 cells expressed heavy molecular weight cytokeratin, p63, and vimentin. The population doubling time was 25.8 hours, and the cells showed fast collective cell migration in a wound-healing assay. Short tandem repeat analysis confirmed it to be derived from the primary tumor of the patient. Next-generation sequencing revealed alterations in cell cycle regulation genes, including inactivating mutations in CDKN2A and TP53 and high-level amplification of CCND1 and EGFR. CAE606 showed a strong decrease of phospo-Rb expression upon exposure to the CDK4/6 inhibitor palbociclib, causing significant growth inhibition with an IC of 0.46 µM.
This is the first report of a stable EAC SCC cell line. Its genetic features make it a useful tool for preclinical testing of new therapeutic agents for EAC SCC, particularly those targeting cell cycle regulation in combination with radio- and chemotherapy or other specific signaling pathway inhibitors.
对源自外耳道鳞状细胞癌（SCC）的CAE606细胞系进行特性分析，并证明其作为测试候选治疗药物模型的实用性。
临床前转化研究。
生物医学研究所。
该细胞系源自中度分化的T2N0M0外耳道SCC。我们研究了其组织学和遗传学特征以及生长和侵袭参数。分析了其对细胞周期蛋白依赖性激酶4/6（CDK4/6）细胞周期抑制剂哌柏西利的敏感性。
CAE606细胞表达高分子量细胞角蛋白、p63和波形蛋白。群体倍增时间为25.8小时，并且在伤口愈合试验中细胞显示出快速的集体细胞迁移。短串联重复序列分析证实它源自患者的原发性肿瘤。下一代测序揭示了细胞周期调控基因的改变，包括CDKN2A和TP53的失活突变以及CCND1和EGFR的高水平扩增。CAE606在暴露于CDK4/6抑制剂哌柏西利后显示磷酸化视网膜母细胞瘤蛋白（phospo-Rb）表达强烈降低，导致显著的生长抑制，IC50为0.46μM。
这是关于稳定的外耳道SCC细胞系的首次报道。其遗传特征使其成为用于外耳道SCC新治疗药物临床前测试的有用工具，特别是那些与放疗、化疗或其他特定信号通路抑制剂联合靶向细胞周期调控的药物。
