Dept. of Thoracic Oncology, Thoraxklinik/University of Heidelberg, Amalienstr. 5, 69126 Heidelberg, Germany.
Lung Cancer. 2012 Jan;75(1):45-57. doi: 10.1016/j.lungcan.2011.05.020.
Cell lines play an important role for studying tumor biology and novel therapeutic agents. Particularly in pulmonary squamous cell carcinoma (SCC) the availability of cell lines is limited and knowledge about their representativeness for corresponding tumor tissue is scanty.
We established three novel SCC cell lines from fresh tumor tissue of 28 donors, including 8 SCC. Two cell lines were derived from different localizations of the same donor, i.e. primary tumor and lymph node metastasis. This represents a so far unique combination in lung cancer. The genotypes, gene expression profiles and mutational status of epidermal growth factor receptor (EGF-R) and Kirsten rat sarcoma (k-ras) of the cell lines and their corresponding tumor tissue were analyzed and compared. Moreover, the molecular characteristics were related to functional properties of the cell lines. Those comprised proliferation, motility and chemosensitivity. The cell lines were authenticated by single tandem repeat DNA typing. Tumorigenicity was analyzed in a murine xenograft model.
Comparative genomic hybridization and multiplex fluorescence in situ hybridization revealed essential genetic similarities between the cell lines and their corresponding tumor tissue, but indicated also some genetic evolution and clonal selection. EGF-R or k-ras mutations were not detected. Gene expression profiling showed various differences between tumor tissue and cell lines affecting gene clusters associated with immune response, adhesion, proliferation, differentiation and angiogenesis. However, there were also common gene expression patterns reflecting the relationship between cell lines and their corresponding tumor tissue. Moreover, the molecular characteristics of the tumor tissue and the descendent cell line were associated with functional properties of the latter. All cell lines showed a unique, heterozygous human DNA profile and one cell line displayed rapid tumor formation in mice.
Here, we demonstrate that cell lines represent a useful in vitro system for studying basic mechanisms in lung cancer, but cover only distinct molecular characteristics of the original tumor. Moreover, we present three novel, comprehensively characterized SCC cell lines.
细胞系在研究肿瘤生物学和新型治疗药物方面发挥着重要作用。特别是在肺鳞状细胞癌（SCC）中，细胞系的可用性有限，并且对其对应肿瘤组织的代表性知之甚少。
我们从 28 位供体的新鲜肿瘤组织中建立了三个新的 SCC 细胞系，其中包括 8 个 SCC。两个细胞系源自同一供体的不同部位，即原发性肿瘤和淋巴结转移。这代表了肺癌中迄今为止独一无二的组合。分析和比较了细胞系及其相应肿瘤组织的表皮生长因子受体（EGF-R）和 Kirsten 大鼠肉瘤（k-ras）的基因型、基因表达谱和突变状态。此外，还将分子特征与细胞系的功能特性相关联。这些特性包括增殖、迁移和化疗敏感性。通过单串联重复 DNA 分型对细胞系进行了鉴定。在小鼠异种移植模型中分析了致瘤性。
比较基因组杂交和多重荧光原位杂交显示细胞系与其相应肿瘤组织之间存在基本的遗传相似性，但也表明存在一些遗传进化和克隆选择。未检测到 EGF-R 或 k-ras 突变。基因表达谱分析显示肿瘤组织和细胞系之间存在各种差异，影响与免疫反应、粘附、增殖、分化和血管生成相关的基因簇。然而，也存在反映细胞系与其相应肿瘤组织之间关系的共同基因表达模式。此外，肿瘤组织和衍生细胞系的分子特征与后者的功能特性相关。所有细胞系均显示出独特的杂合人 DNA 图谱，其中一个细胞系在小鼠中迅速形成肿瘤。
在这里，我们证明细胞系是研究肺癌基础机制的有用体外系统，但仅涵盖原始肿瘤的特定分子特征。此外，我们还提供了三个新的、全面表征的 SCC 细胞系。
