一种新型人乳头瘤病毒 16 型阳性扁桃体癌细胞系，对辐射和顺铂高度敏感。
A novel human in vitro papillomavirus type 16 positive tonsil cancer cell line with high sensitivity to radiation and cisplatin.
机构信息
Department of Laboratory Medicine, Division of Medical Microbiology, Skane Laboratory Medicine, Lund University, Lund, Sweden.
Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Skane University Hospital, Barngatan 4, SE-222 25, Lund, Sweden.
出版信息
BMC Cancer. 2019 Mar 25;19(1):265. doi: 10.1186/s12885-019-5469-8.
BACKGROUND
Human papillomavirus (HPV) is an established risk factor for oropharyngeal squamous cell carcinoma (OSCC). The aim was to establish cell lines from HPV-positive tonsil carcinomas to be used for treatment development.
METHODS
Fresh samples from 23 HPV-positive tonsil carcinomas were cultivated in vitro. The established cell line was analyzed for viral characteristics, cell karyotype, TP53 status, and growth capabilities in nude mice. In vitro studies of sensitivities to radiation, cisplatin and cetuximab were performed.
RESULTS
After 19 months (eight passages), one cell line, LU-HNSCC-26, was established in vitro and also grew as xenografts. The tumor was from a 48 year old non-smoking man with non-keratinizing, p16 positive tonsil OSCC, stage T2N0M0 with HPV16. It contained 19.5 (CV% 3.7) HPV16 copies/cell (passage 8). The complete HPV16 genome sequence was obtained. Episomal HPV16 was present with an E2/E7 ratio of 1.1 (CV% 2.6). In addition, HPV16 mRNA specific for the intact E2 gene was detected. The viral expression manifested 1.0 (CV% 0.1) E7 mRNA copies per HPV16 genome. The karyotype was determined and the cell line demonstrated wild type TP53. The ID50 for radiation was 0.90 Gy and the IC50 for cisplatin was 0.99 μmol/L. The cell line was inhibited to a maximum of 18% by cetuximab.
CONCLUSIONS
We established an in vitro tonsil carcinoma cell line containing episomal HPV16. This is an important step towards efficient treatment development.
背景
人乳头瘤病毒（HPV）是口咽鳞状细胞癌（OSCC）的既定危险因素。目的是建立 HPV 阳性扁桃体癌的细胞系，用于治疗开发。
方法
从 23 例 HPV 阳性扁桃体癌的新鲜样本中进行体外培养。对建立的细胞系进行病毒特征、细胞染色体核型、TP53 状态和裸鼠生长能力的分析。进行体外对辐射、顺铂和西妥昔单抗敏感性的研究。
结果
经过 19 个月（八代），在体外建立了一个细胞系 LU-HNSCC-26，并作为异种移植物生长。该肿瘤来自一位 48 岁的非吸烟男性，患有非角化、p16 阳性的扁桃体 OSCC，分期为 T2N0M0，HPV16 阳性。它含有 19.5（CV%3.7）个 HPV16 拷贝/细胞（第 8 代）。获得了完整的 HPV16 基因组序列。存在游离的 HPV16，E2/E7 比值为 1.1（CV%2.6）。此外，还检测到完整 E2 基因的 HPV16 mRNA。病毒表达表现为每个 HPV16 基因组 1.0（CV%0.1）个 E7 mRNA 拷贝。确定了染色体核型，细胞系显示野生型 TP53。辐射的 ID50 为 0.90Gy，顺铂的 IC50 为 0.99μmol/L。西妥昔单抗最大抑制率为 18%。
结论
我们建立了含有游离 HPV16 的体外扁桃体癌细胞系。这是向有效治疗开发迈出的重要一步。
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