Welch D R, Krizman D B, Nicolson G L
Clin Exp Metastasis. 1984 Oct-Dec;2(4):333-55. doi: 10.1007/BF00135172.
The properties of cell clones derived from locally growing and spontaneous metastases of 13762NF mammary adenocarcinoma change during in vitro growth. This has been termed phenotypic drift and is reproducible in independent experiments using different cryoprotected cell stocks. To determine whether phenotypic drift in 13762NF cell clones is the result of an en bloc shift in the properties of all tumor cells, or independent phenotypic divergence of tumor cells to produce a mixed cell population, local tumor-derived clone MTF7 was subcloned at low and high culture passage numbers in vitro. Each subclone was analyzed in vitro for cell morphology, growth rate, saturation density, karyotype and ploidy, and in vivo for experimental metastatic behavior. Subclones derived from low passage clone MTF7 (T11; tissue culture passage number 11) were relatively homogeneous in their growth rates (doubling times of 16.8-17.4 h) and saturation densities (approximately 2 X 10(5) cells/cm2); yet, these same subclones were heterogeneous in their in vitro cell morphologies, experimental metastatic potentials (means range from 0 to greater than 100 tumor nodules per lung), size distributions of lung tumor nodules, marker chromosomes and modal chromosome numbers. High passage MTF7 (T35; tissue culture passage number 35) subclones had similar growth rates and saturation densities, except for subclone 2, which had a doubling time of approximately 26 h. Cell morphologies, experimental metastatic potentials (means range from 3 to greater than 600 tumor nodules per lung), size distribution of lung tumor nodules, marker chromosomes and modal chromosome numbers varied between MTF7 (T35) subclones. The results suggest that simultaneous, independent divergence of several phenotypes from a single cloned cell occurred to form a mixed cell population containing cells with independently segregated, unrelated phenotypes. Thus, the reproducibility of phenotypic drift in clonal cell populations was probably the result of tumor cell divergence and was not an en bloc shift in phenotypic properties of all cells.
源自13762NF乳腺腺癌局部生长和自发转移灶的细胞克隆在体外生长过程中特性会发生改变。这被称为表型漂移，并且在使用不同冷冻保护细胞株的独立实验中可重复出现。为了确定13762NF细胞克隆中的表型漂移是所有肿瘤细胞特性整体转变的结果，还是肿瘤细胞独立的表型分化以产生混合细胞群体，将源自局部肿瘤的克隆MTF7在体外低传代和高传代培养时进行亚克隆。对每个亚克隆进行体外细胞形态、生长速率、饱和密度、核型和倍性分析，以及体内实验性转移行为分析。源自低传代克隆MTF7（T11；组织培养传代数11）的亚克隆在生长速率（倍增时间为16.8 - 17.4小时）和饱和密度（约2×10⁵个细胞/cm²）方面相对均一；然而，这些相同的亚克隆在体外细胞形态、实验性转移潜能（每肺平均肿瘤结节数范围从0到大于100个）、肺肿瘤结节大小分布、标记染色体和众数染色体数方面存在异质性。高传代MTF7（T35；组织培养传代数35）亚克隆具有相似的生长速率和饱和密度，但亚克隆2除外，其倍增时间约为26小时。MTF7（T35）亚克隆之间的细胞形态、实验性转移潜能（每肺平均肿瘤结节数范围从3到大于600个）、肺肿瘤结节大小分布、标记染色体和众数染色体数各不相同。结果表明，从单个克隆细胞同时发生了几种表型的独立分化，形成了一个包含具有独立分离、不相关表型细胞的混合细胞群体。因此，克隆细胞群体中表型漂移的可重复性可能是肿瘤细胞分化的结果，而不是所有细胞表型特性的整体转变。
