Early origin and pervasiveness of cellular heterogeneity in some malignant transformations.
Early origin and pervasiveness of cellular heterogeneity in some malignant transformations.
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一些恶性转化中细胞异质性的早期起源和普遍性。
DOI：
10.1073/pnas.81.16.5121
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发表时间：
1984
影响因子：
11.1
通讯作者：
Rubin,H
中科院分区：
文献类型：
--
作者：
Rubin,H
每周在塑料培养皿上的单层培养物中传代未转化的BALB/3 T3细胞，并在悬浮于琼脂中时定期测定等分试样的集落产生。在几个月的传代过程中，在琼脂试验中出现一次单个大菌落，并分离其组成细胞以形成转化细胞的亚系。这些细胞具有转化细胞的梭形和圆形形态特征，在琼脂中的集落形成效率（CFEag）约为10%。随机分离5个琼脂集落，并进一步分析这些初级亚克隆的细胞群。五个亚克隆种群中有四个在外观上略有不同，但一致，而第五个有一个显着不同的殖民地形态。它们在CFEag以及琼脂菌落的平均直径方面也彼此不同。尽管CFEag和菌落大小在每周重复转移中发生了明显变化，但五个亚克隆之间的这些一般差异仍然存在。所有的亚克隆都在裸鼠体内产生了肉瘤，但产生的速度不同。第二代的五个亚克隆来自每三个原始的亚克隆群体。所有次级亚克隆具有与它们所来源的初级亚克隆相同的形态。来自每个亚克隆的次级亚克隆的CFEag和菌落大小的平均值作为一个组与其他组不同，但它们之间也存在较小程度的差异。尽管主要亚克隆在形态、琼脂生长和小鼠肿瘤产生方面存在差异，但它们在塑料表面上的快速生长速率几乎相同，并且都具有高葡萄糖消耗速率。第二个转化的克隆出现在连续传代的非转化细胞5个月后，第一个已经出现。该克隆的亚克隆在形态学或CFEag方面彼此没有明显差异。结果表明，可识别的异质性可以出现在一些肿瘤在其发展的最早阶段，并涉及其组成细胞的高比例，而它可能不会成为明显的其他肿瘤，直到很久以后。
Nontransformed BALB/3T3 cells were passaged weekly in monolayer culture on plastic dishes and aliquots were regularly assayed for colony production when suspended in agar. During several months of passaging, a single large colony arose once in the agar assay, and its constituent cells were isolated to form a subline of transformed cells. These cells had the fusiform and rounded morphologies characteristic of transformed cells and had a colony-forming efficiency in agar (CFEag) of approximately 10%. Five of the agar colonies were isolated at random and the cell populations of these primary subclones were further analyzed. Four of the five subclonal populations differed from each other in appearance slightly, but consistently, while the fifth had a markedly different colonial morphology. They also differed from one another in CFEag as well as in average diameter of the agar colonies. These general differences among the five subclones remained, although the CFEag and colony sizes changed recognizably in repeated weekly transfers. All of the subclones produced sarcomas in nude mice but did so at different rates. A secondary generation of five subclones was derived from each of three of the original subclonal populations. All the secondary subclones had the same morphology as the primary subclones from which they were derived. The averages of the CFEag and colony sizes of the secondary subclones from each of the subclones differed as a group from the other groups, but they also differed, to a lesser extent, among themselves. Despite the differences noted among the primary subclones in morphology, growth in agar, and tumor production in mice, they were virtually identical in their rapid growth rate on a plastic surface and all shared a high rate of glucose consumption. A second transformed clone arose among the continuously passaged nontransformed cells 5 months after the first one had appeared. Subclones of this clone did not differ recognizably from one another in morphology or in CFEag. The results indicate that recognizable heterogeneity can arise in some tumors during the earliest stages of their development and involve a high proportion of their constituent cells, while it may not become evident in other tumors until much later.