Tsao M S, Grisham J W
Cancer Res. 1987 Mar 1;47(5):1282-6.
From nine clonal subpopulations (strains) of chemically transformed cultured rat hepatic epithelial cells which were tumorigenic when implanted into 1-day-old isogeneic rats, a cell line was reestablished from each tumor and the cellular properties of the tumor-derived cell lines were compared to those of the corresponding progenitor cells that were implanted to produce the tumors. In seven of eight instances, the cellular DNA content of the tumor-derived cells was virtually identical to the DNA content of the respective progenitor cells, but in one case the tumor cells had twice as much DNA as did their progenitor cells. During the development of tumors in vivo, other cellular phenotypic properties often underwent considerable, but variable changes. These changes included the activity of gamma-glutamyl transpeptidase, the growth properties on plastic surfaces, and the expression of LDH isozymes. Although there was a relative enhancement in the ability of most of the tumor-derived cells to proliferate or to form colonies in calcium-poor medium, several tumor-derived cell lines had very low colony-forming efficiencies in media containing either normal or low levels of calcium. The most consistent association between phenotypes expressed in vitro and tumorigenicity was the ability of cells to form colonies in soft agar; all tumor-derived lines expressed this phenotype, and with some of them this phenotype was acquired only during the process of tumor formation in vivo. These results demonstrate that further phenotypic and genotypic alterations may occur in vivo during tumor formation by chemically transformed cultured cells following their implantation into isogeneic animals; and some of the alterations that occur in vivo may be necessary for the complete expression of tumorigenicity. Although anchorage-independent growth capacity cannot be used to predict the tumorigenicity of clones of rat liver epithelial cells chemically transformed in vitro, this growth property appears to be invariably induced prior to or during the formation of tumors in vivo by these cells.
从化学转化的培养大鼠肝上皮细胞的九个克隆亚群（菌株）中，当将其植入1日龄同基因大鼠时具有致瘤性，从每个肿瘤中重新建立细胞系，并将肿瘤衍生细胞系的细胞特性与植入以产生肿瘤的相应祖细胞的特性进行比较。在八个实例中的七个中，肿瘤衍生细胞的细胞DNA含量与各自祖细胞的DNA含量几乎相同，但在一个实例中，肿瘤细胞的DNA是其祖细胞的两倍。在体内肿瘤发展过程中，其他细胞表型特性经常发生相当大但可变的变化。这些变化包括γ-谷氨酰转肽酶的活性、在塑料表面上的生长特性以及LDH同工酶的表达。尽管大多数肿瘤衍生细胞在低钙培养基中增殖或形成集落的能力相对增强，但几个肿瘤衍生细胞系在含有正常或低水平钙的培养基中的集落形成效率非常低。体外表达的表型与致瘤性之间最一致的关联是细胞在软琼脂中形成集落的能力；所有肿瘤衍生系都表达这种表型，并且其中一些仅在体内肿瘤形成过程中才获得这种表型。这些结果表明，化学转化的培养细胞植入同基因动物体内后，在肿瘤形成过程中可能会发生进一步的表型和基因型改变；并且体内发生的一些改变可能是致瘤性完全表达所必需的。虽然不依赖贴壁的生长能力不能用于预测体外化学转化的大鼠肝上皮细胞克隆的致瘤性，但这种生长特性似乎总是在这些细胞体内肿瘤形成之前或期间被诱导。
