Trainer D L, Wheelock E F
Cancer Res. 1984 Mar;44(3):1063-71.
We evaluated the phenotypic changes that take place in the L5178Y tumor cell population during the establishment, maintenance, and termination of the L5178Y tumor-dormant state in DBA/2 mice. Since there is considerable variation among DBA/2 mice in the course of the L5178Y tumor-dormant state, analysis of these phenotypic changes required prospective studies on individual mice. Therefore, we developed a partial peritoneal lavage technique which could be performed repeatedly on an individual mouse without killing the mouse and without terminating the tumor-dormant state. The partial peritoneal lavage technique provided cell samples that were quantitatively representative of the entire peritoneal cell contents without altering the relative proportions or total number of host peritoneal cell subpopulations. Tumor cell clones were isolated from the uncloned L5178Y cell inoculum that was used to initiate the tumor-dormant state, and from the partial peritoneal lavage performed on individual mice at regular intervals throughout the tumor-dormant state until each mouse developed an ascitic tumor. We found that the uncloned L5178Y cell population is heterogeneous, with the majority of the cells [approximately 80% of the clonal populations ("original" phenotype)] able to compete as well as the uncloned L5178Y cell population for immune cytolytic T-lymphocyte activity, and a smaller percentage [approximately 20% of the clones ("emergent" phenotype)] competing significantly less but similar to the tumor cell population which grows out as an ascitic tumor at the termination of the tumor-dormant state. However, both "original" and "emergent" phenotypes encompass a range of subpopulations which have the respective characteristics. There was a progressive enrichment in the tumor cell population for "emergent"-phenotype cells as mice progressed through the tumor-dormant state. In the 30-day period prior to tumor emergence, only "emergent"-phenotype cell clones were isolated. These data indicate that, during the course of the tumor-dormant state, there is continual selection by immune cytolytic T-lymphocytes for "emergent"-phenotype cells, which preexist in the L5178Y cell population used to initiate the tumor-dormant state, and that the progressive enrichment of "emergent"-phenotype cells in the peritoneal cavity is associated with and may be responsible for termination of the tumor-dormant state.
我们评估了在DBA/2小鼠中建立、维持和终止L5178Y肿瘤休眠状态期间L5178Y肿瘤细胞群体发生的表型变化。由于DBA/2小鼠在L5178Y肿瘤休眠状态过程中存在相当大的差异，对这些表型变化的分析需要对个体小鼠进行前瞻性研究。因此，我们开发了一种部分腹膜灌洗技术，该技术可以在不杀死小鼠且不终止肿瘤休眠状态的情况下对个体小鼠重复进行。部分腹膜灌洗技术提供的细胞样本在数量上代表了整个腹膜细胞内容物，而不会改变宿主腹膜细胞亚群的相对比例或总数。从用于启动肿瘤休眠状态的未克隆L5178Y细胞接种物中，以及在整个肿瘤休眠状态期间定期对个体小鼠进行的部分腹膜灌洗中分离肿瘤细胞克隆，直到每只小鼠出现腹水肿瘤。我们发现未克隆的L5178Y细胞群体是异质的，大多数细胞[约80%的克隆群体（“原始”表型）]在免疫细胞溶解T淋巴细胞活性方面与未克隆的L5178Y细胞群体竞争能力相同，而较小比例[约20%的克隆（“新出现”表型）]竞争能力明显较弱，但与在肿瘤休眠状态终止时以腹水肿瘤形式生长的肿瘤细胞群体相似。然而，“原始”和“新出现”表型都包含一系列具有各自特征的亚群。随着小鼠经历肿瘤休眠状态，肿瘤细胞群体中“新出现”表型细胞逐渐富集。在肿瘤出现前的30天内，仅分离出“新出现”表型细胞克隆。这些数据表明，在肿瘤休眠状态过程中，免疫细胞溶解T淋巴细胞持续选择“新出现”表型细胞，这些细胞在用于启动肿瘤休眠状态的L5178Y细胞群体中预先存在，并且“新出现”表型细胞在腹腔中的逐渐富集与肿瘤休眠状态的终止相关，并且可能是其原因。
