Tilgen W, Boukamp P, Breitkreutz D, Dzarlieva R T, Engstner M, Haag D, Fusenig N E
Cancer Res. 1983 Dec;43(12 Pt 1):5995-6011.
Two cell lines (SCL-I and SCL-II) derived from squamous cell carcinomas of human skin were investigated during 4 years in culture. Both lines were tumorigenic in nude mice, and cells could be recultivated from xenografts. Growth in agar remained poor, but both cell lines developed abnormal stratified epithelial structures in organotypical cultures. The morphological and particularly ultrastructural characteristics remained typical in both cultures and xenografts. Keratinization slightly decreased, but nude mouse tumors differentiated as the original tumors, and this was reflected in keratin expression. Six major polypeptides (Mr 61,000, 57,000, 54,000, 51,000, 49,000, and 45,000) were similarly identified in both tumors and cell lines, also after animal passage, which was further substantiated by two-dimensional gel electrophoresis, but quantitative variations were found with different growth conditions. A distinct keratin cytoskeletal network was visualized in both lines by immunofluorescence, but only a few cells in SCL-II also expressed vimentin. Flow cytometry demonstrated 2c DNA stem lines for original tumors and derived lines. Early passages were hypodiploid by cytogenetic analysis of banded chromosomes. In SCL-I, a shift to tetraploidy occurred before passage 20 and remained stable throughout. In SCL-II, an incomplete shift to near tetraploidy and a stem line deviation were apparent, but later passages, nude mouse tumors, and cells recultured therefrom were hypodiploid (2c) again. Chromosome studies further revealed distinct stable marker chromosomes which showed additional structural aberrations with time in culture and after animal passage. Thus, phenotypically and genotypically, each squamous cell carcinoma and its derived cell line were distinct, and characteristics were preserved over long time periods in vitro and through in vivo passage.
对源自人皮肤鳞状细胞癌的两种细胞系(SCL-I和SCL-II)进行了4年的培养研究。这两种细胞系在裸鼠中均具有致瘤性,并且可以从异种移植瘤中再次培养细胞。在琼脂中生长仍然不佳,但两种细胞系在器官型培养中都形成了异常的分层上皮结构。在两种培养物和异种移植瘤中,形态学特征尤其是超微结构特征仍然保持典型。角质化略有降低,但裸鼠肿瘤与原始肿瘤一样发生分化,这在角蛋白表达中得到体现。在肿瘤和细胞系中,同样鉴定出六种主要多肽(分子量分别为61,000、57,000、54,000、51,000、49,000和45,000),在动物传代后也是如此,二维凝胶电泳进一步证实了这一点,但在不同生长条件下发现了定量变化。通过免疫荧光在两种细胞系中都观察到了明显的角蛋白细胞骨架网络,但只有SCL-II中的少数细胞也表达波形蛋白。流式细胞术显示原始肿瘤及其衍生细胞系的DNA干细胞系为2c。通过对带型染色体的细胞遗传学分析,早期传代的细胞为亚二倍体。在SCL-I中,在第20代之前发生了向四倍体的转变,并在整个过程中保持稳定。在SCL-II中,向近四倍体的不完全转变和干细胞系偏差很明显,但后期传代、裸鼠肿瘤以及从中重新培养的细胞再次变为亚二倍体(2c)。染色体研究进一步揭示了明显稳定的标记染色体,这些染色体在培养过程中和动物传代后随时间显示出额外的结构畸变。因此,在表型和基因型上,每种鳞状细胞癌及其衍生的细胞系都是不同的,并且其特征在体外长时间以及通过体内传代得以保留。