Prostate Cancer Research Centre, University College London, London, UK.
Cell Biol Toxicol. 2012 Oct;28(5):291-301. doi: 10.1007/s10565-012-9224-z. Epub 2012 Jul 12.
Primary cultures and cell lines form three types of colonies, termed holoclones, meroclones and paraclones by Barrandon and Green (Proc Natl Acad Sci U S A 84:2302-2306, 1987). They suggested that the three types correspond to colonies derived from stem, transit-amplifying and terminally differentiated cells. We determined the effect of culture conditions (seeding density, serum concentration, type of medium and substrate) on the proportion of each colony type and the cell number of individual colonies, using three prostate cancer cell lines, DU145, LNCaP and PC-3. In less favourable culture conditions, stem cell (SC) colonies tended to be lost; but in more favourable conditions, only modest increases in the proportion of SC colonies were observed. Under some conditions, cell number, but not colony-forming ability, was altered, indicating that colony cell number is controlled, at least in part, by different factors to colony formation. Colony-forming ability of individual cell lines is remarkably stable and there is little evidence for clonal evolution in culture, which might be expected and would result in more aggressive, faster-growing cells. Better understanding of how colony-forming efficiency is controlled could lead to the identification of drug targets that control SC growth and modify the progression of cancer.
巴兰登和格林（Proc Natl Acad Sci U S A 84:2302-2306, 1987）将原代培养物和细胞系形成的三种类型的集落分别称为全能克隆、中间型克隆和局限型克隆。他们认为这三种类型分别对应于由干细胞、过渡扩增细胞和终末分化细胞衍生而来的集落。我们使用三种前列腺癌细胞系 DU145、LNCaP 和 PC-3，通过确定培养条件（接种密度、血清浓度、培养基类型和底物）对每种集落类型的比例和单个集落的细胞数量的影响，来确定培养条件对这三种集落类型的影响。在不太有利的培养条件下，干细胞（SC）集落往往会丢失；但在更有利的条件下，仅观察到 SC 集落比例适度增加。在某些条件下，细胞数量发生了变化，但集落形成能力没有改变，这表明集落细胞数量的控制至少部分是由不同的因素来控制的。单个细胞系的集落形成能力非常稳定，几乎没有证据表明在培养过程中存在克隆进化，这可能是预期的结果，并且会导致更具攻击性、生长更快的细胞。更好地了解集落形成效率是如何控制的，可能会发现控制干细胞生长的药物靶点，并改变癌症的进展。
