Feng Helin, Tillman Heather, Wu Gang, Davidoff Andrew M, Yang Jun
Department of Orthopedics, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei, People's Republic of China.
Department of Pathology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Oncotarget. 2018 Jun 5;9(43):27087-27091. doi: 10.18632/oncotarget.25484.
Osteosarcoma (OS) cell lines are widely used in understanding the biological functions of cancer, identification and validation of therapeutic targets, as well as or preclinical drug screening. Here we report there is a frequent loss-of-function of polycomb repressive complex 2 (PRC2) in OS cell lines but it is rare in tumor samples based on genomic sequencing data, western blotting and immunohistochemistry analysis of H3K27me3. U2OS and 143B cell lines have a complete loss of function of PRC2 and several others have partial loss. In OS tumor tissues, only 1 out of 14 has low expression of H3K27me3. Kaplan-Meier analysis indicates that high EZH2, the component of PRC2, is associated with poor metastasis-free survival. Our observations are to raise the alarm that particular caution should be taken when using OS cell line models to study the disease, functional genomics, therapeutic target validation, drug screening, and epigenetic studies. Nevertheless, these cell lines will become useful biological tools to dissect the functions of PRC2.
骨肉瘤（OS）细胞系被广泛用于了解癌症的生物学功能、治疗靶点的鉴定与验证以及临床前药物筛选。在此我们报告，基于基因组测序数据、蛋白质免疫印迹法以及H3K27me3的免疫组织化学分析，在OS细胞系中多梳抑制复合物2（PRC2）功能缺失频繁，但在肿瘤样本中却很少见。U2OS和143B细胞系PRC2功能完全丧失，其他几个细胞系则部分丧失。在OS肿瘤组织中，14个样本中只有1个H3K27me3表达较低。Kaplan-Meier分析表明，PRC2的组成成分EZH2高表达与无转移生存期较差相关。我们的观察结果警示，在使用OS细胞系模型研究该疾病、功能基因组学、治疗靶点验证、药物筛选以及表观遗传学研究时应格外谨慎。尽管如此，这些细胞系将成为剖析PRC2功能的有用生物学工具。
