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人肺癌细胞系及其相应肿瘤的特征比较。

Comparison of features of human lung cancer cell lines and their corresponding tumors.

作者信息

Wistuba I I, Bryant D, Behrens C, Milchgrub S, Virmani A K, Ashfaq R, Minna J D, Gazdar A F

机构信息

Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas 75235, USA.

出版信息

Clin Cancer Res. 1999 May;5(5):991-1000.

Abstract

Although human lung tumor-derived cell lines play an important role in the investigation of lung cancer biology and genetics, there is no comprehensive study comparing the genotypic and phenotypic properties of lung cancer cell lines with those of the individual tumors from which they were derived. We compared a variety of properties of 12 human non-small cell lung carcinoma (NSCLC) cell lines (cultured for a median period of 39 months; range, 12-69) and their corresponding archival tumor tissues. There was, in general, an excellent concordance between the lung tumor cell lines and their corresponding tumor tissues for morphology (100%), the presence of aneuploidy (100%), immunohistochemical expression of HER2/neu (100%) and p53 proteins (100%), loss of heterozygosity at 13 chromosomal regions analyzed (97%) using 37 microsatellite markers, microsatellite alterations (MAs, 75%), TP53 (67%), and K-ras (100%) gene mutations. In addition, there was 100% concordance for the parental allele lost in all 115 comparisons of allelic losses. Some discrepancies were found; more aneuploid subpopulations of cells were detected in the cell lines as well as higher incidences of TP53 mutations (4 of 10 mutations not found in the tumors) and microsatellite alterations (two cell lines with MAs not detected in the tumors). Similar loss of heterozygosity frequencies by chromosomal regions and mean fractional allelic loss index were detected between successfully cultured and 40 uncultured lung tumors (0.45 and 0.49, respectively), indicating that both groups were similar. Our findings indicate that the NSCLC cell lines in the large majority of instances retain the properties of their parental tumors for lengthy culture periods. NSCLC cell lines appear very representative of the lung cancer tumor from which they were derived and thus provide suitable model systems for biomedical studies of this important neoplasm.

摘要

尽管人肺肿瘤来源的细胞系在肺癌生物学和遗传学研究中发挥着重要作用,但尚无全面研究比较肺癌细胞系与其所源自的个体肿瘤的基因型和表型特性。我们比较了12个人非小细胞肺癌(NSCLC)细胞系(培养中位时间为39个月;范围为12 - 69个月)及其相应存档肿瘤组织的多种特性。总体而言,肺肿瘤细胞系与其相应肿瘤组织在形态学(100%)、非整倍体存在情况(100%)、HER2/neu(100%)和p53蛋白的免疫组化表达(100%)、使用37个微卫星标记分析的13个染色体区域的杂合性缺失(97%)、微卫星改变(MAs,75%)、TP53(67%)以及K-ras(100%)基因突变方面具有极好的一致性。此外,在所有115次等位基因缺失比较中,亲本等位基因丢失情况的一致性为100%。也发现了一些差异;在细胞系中检测到更多的非整倍体细胞亚群,以及更高的TP53突变发生率(肿瘤中未发现的10个突变中有4个)和微卫星改变(两个细胞系的MAs在肿瘤中未检测到)。在成功培养的和40个未培养的肺肿瘤之间检测到相似的按染色体区域的杂合性缺失频率和平均等位基因丢失分数指数(分别为0.45和0.49),表明两组相似。我们的研究结果表明,在大多数情况下,NSCLC细胞系在长时间培养过程中保留了其亲本肿瘤的特性。NSCLC细胞系似乎非常能代表其所源自的肺癌肿瘤,因此为这种重要肿瘤的生物医学研究提供了合适的模型系统。

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