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一组独特的患者源性皮肤鳞状细胞癌细胞系为治疗性测试提供了临床前途径。

A Unique Panel of Patient-Derived Cutaneous Squamous Cell Carcinoma Cell Lines Provides a Preclinical Pathway for Therapeutic Testing.

机构信息

Blizard Institute, Barts and the London School of Medicine and Dentistry, QMUL, London E1 2AT, UK.

Barts Cancer Institute, QMUL, London EC1M 6BQ, UK.

出版信息

Int J Mol Sci. 2019 Jul 12;20(14):3428. doi: 10.3390/ijms20143428.

Abstract

BACKGROUND

Cutaneous squamous cell carcinoma (cSCC) incidence continues to rise with increasing morbidity and mortality, with limited treatment options for advanced disease. Future improvements in targeted therapy will rely on advances in genomic/transcriptomic understanding and the use of model systems for basic research. We describe here the panel of 16 primary and metastatic cSCC cell lines developed and characterised over the past three decades in our laboratory in order to provide such a resource for future preclinical research and drug screening.

METHODS

Primary keratinocytes were isolated from cSCC tumours and metastases, and cell lines were established. These were characterised using short tandem repeat (STR) profiling and genotyped by whole exome sequencing. Multiple in vitro assays were performed to document their morphology, growth characteristics, migration and invasion characteristics, and in vivo xenograft growth.

RESULTS

STR profiles of the cSCC lines allow the confirmation of their unique identity. Phylogenetic trees derived from exome sequence analysis of the matched primary and metastatic lines provide insight into the genetic basis of disease progression. The results of in vivo and in vitro analyses allow researchers to select suitable cell lines for specific experimentation.

CONCLUSIONS

There are few well-characterised cSCC lines available for widespread preclinical experimentation and drug screening. The described cSCC cell line panel provides a critical tool for in vitro and in vivo experimentation.

摘要

背景

皮肤鳞状细胞癌(cSCC)的发病率持续上升,发病率和死亡率不断增加,晚期疾病的治疗选择有限。未来靶向治疗的进展将依赖于基因组/转录组理解的进步和基础研究模型系统的使用。我们在这里描述了过去三十年来在我们实验室中开发和表征的 16 种原发性和转移性 cSCC 细胞系,以便为未来的临床前研究和药物筛选提供这样的资源。

方法

从 cSCC 肿瘤和转移灶中分离原代角质形成细胞,并建立细胞系。这些细胞系通过短串联重复(STR)分析进行特征分析,并通过全外显子组测序进行基因分型。进行了多种体外检测,以记录它们的形态、生长特征、迁移和侵袭特征以及体内异种移植物生长。

结果

cSCC 系的 STR 谱可确认其独特的身份。来自匹配的原发性和转移性系的外显子组序列分析得出的系统发育树提供了疾病进展遗传基础的深入了解。体内和体外分析的结果允许研究人员为特定实验选择合适的细胞系。

结论

可用于广泛的临床前实验和药物筛选的特征良好的 cSCC 系很少。描述的 cSCC 细胞系面板为体外和体内实验提供了重要工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/235c/6678499/b833bc398807/ijms-20-03428-g001.jpg

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