Pluripotent embryonal carcinoma clones derived from the human teratocarcinoma cell line Tera-2. Differentiation in vivo and in vitro.
Pluripotent embryonal carcinoma clones derived from the human teratocarcinoma cell line Tera-2. Differentiation in vivo and in vitro.
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发表时间：
1984-02
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通讯作者：
P. Andrews;I. Damjanov;D. Simon;G. Banting;C. Carlin;N. Dracopoli;J. Fogh
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作者：
P. Andrews;I. Damjanov;D. Simon;G. Banting;C. Carlin;N. Dracopoli;J. Fogh
我们已经从畸胎瘤细胞系Tera-2的异种移植瘤中获得了单细胞克隆，并对其进行了表征。同工酶和染色体分析证实了它们的共同起源。当克隆的培养物保持在高细胞密度时，许多细胞表现出典型的人胚胎癌细胞的形态和细胞表面抗原表型。这些特征包括高的核质比、突出的核仁和球系糖脂抗原SSEA-3的表达。此外，其他细胞，在许多方面类似于这些典型的胚胎癌细胞，是由一个显着的倾向，积累细胞质糖原区分。在Tera-2本身的低传代培养物中观察到类似的细胞以及更分化的细胞。当克隆在低细胞密度下生长时，许多细胞呈现更大、更平坦的形状，少数具有多个核仁。此外，岩藻糖基化乳糖胺抗原SSEA-1出现在一些细胞上，而SSEA-3和HLA-A、B、C的表达倾向于降低。通常纤维连接蛋白的合成增加。然而，没有明显的细胞质分化后，超微结构检查，和人绒毛膜促性腺激素，甲胎蛋白，层粘连蛋白的合成没有检测到。与在培养中观察到的有限的自发变化相反，在将细胞注射到无胸腺（nu/nu）小鼠中后获得的肿瘤中发生了显著的分化。除了胚胎癌细胞，这些肿瘤还含有各种体细胞组织，包括可能与原肠有关的腺体结构和神经成分。这些来源于Tera-2的细胞系构成了克隆人胚胎癌细胞的第一个例子，适应于体外生长，保留了分化成不同体细胞组织的能力。
We have derived and characterized single cell clones from a xenograft tumor of the teratocarcinoma cell line Tera-2. Isozyme and chromosomal analyses confirmed their common origin. When cultures of the clones were maintained at a high cell density, many cells exhibited a morphology and cell surface antigen phenotype typical of human embryonal carcinoma cells. These features included a high nucleo-cytoplasmic ratio, prominent nucleoli, and the expression of the globoseries glycolipid antigen SSEA-3. In addition, other cells, in many respects resembling these typical embryonal carcinoma cells, were distinguished by a marked tendency to accumulate cytoplasmic glycogen. Similar cells, together with more differentiated cells, were seen in low passage cultures of Tera-2 itself. When the clones were grown at a low cell density many cells assumed a larger, flatter shape, a few with multiple nucleoli. Also, the fucosylated lactosamine antigen SSEA-1 appeared on some cells, whereas expression of SSEA-3 and HLA-A,B,C tended to be reduced. Often the synthesis of fibronectin was increased. However, no obvious cytoplasmic differentiation was seen upon ultrastructural examination, and synthesis of human chorionic gonadotropin, alpha-fetoprotein, and laminin was not detected. In contrast to the limited spontaneous changes seen in culture, marked differentiation occurred in tumors obtained following injection of the cells into athymic (nu/nu) mice. In additional to embryonal carcinoma cells, these tumors contained a variety of somatic tissues that included glandular structures, possibly related to the primitive gut, and neural elements. These cell lines derived from Tera-2 constitute the first example of clonal human embryonal carcinoma cells, adapted to growth in vitro, that have retained the capacity for differentiation into diverse somatic tissues.