Retention of intrinsic stem cell hierarchies in carcinoma-derived cell lines
Retention of intrinsic stem cell hierarchies in carcinoma-derived cell lines
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DOI：
10.1158/0008-5472.can-05-0931
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发表时间：
2005-10-01
期刊：
影响因子：
11.2
通讯作者：
Mackenzie, IC
中科院分区：
文献类型：
--
作者：
Locke, M;Heywood, M;Mackenzie, IC
最近的研究表明，癌症的生长和行为最终是由一小部分恶性干细胞亚群决定的，迫切需要有关这些细胞特性的信息，以使它们能够靶向治疗消除。正常干细胞的一个关键特征是它们的不对称分裂，这种机制允许干细胞自我更新，同时产生形成组织主体的扩增和分化细胞等级。大多数癌症死亡是由上皮性恶性肿瘤引起的，但上皮性恶性肿瘤中正常上皮的分层增殖干细胞和扩增细胞模式在多大程度上被保留尚不清楚。在这里，我们表明，即使是由癌细胞产生的细胞系，也始终如一地产生体外集落模式，出乎意料地与正常上皮细胞的干细胞和扩增细胞产生的集落模式相似。从形成的不同类型的集落形态，可以预测其组成细胞的生长潜力及其大分子表达模式。在细胞系传代过程中，干细胞亚群的维持表明，不对称分裂的关键干细胞特性仍然存在，但转向增强干细胞自我更新。恶性上皮干细胞在体内的存在已经通过原发癌细胞的连续移植得到证实，目前的观察表明，即使在细胞系中，干细胞模式也是稳健的，并且持续存在。对这种行为的理解将有助于对恶性干细胞存活的分子或药理学操作的研究。
Recent work indicates that the growth and behavior of cancers are ultimately determined by a small subpopulation of malignant stem cells and that information about the properties of these cells is urgently needed to enable their targeting for therapeutic elimination. A key feature of normal stem cells is their asymmetrical division, the mechanism that allows stem cell self-renewal while producing hierarchies of amplifying and differentiating cells that form the bulk of the tissue. Most cancer deaths result from epithelial malignancies, but the extent to which the hierarchical proliferative stem and amplifying cell patterns of normal epithelia are actually retained in epithelial malignancies has been unclear. Here we show that even cell lines generated from carcinomas consistently produce in vitro colony patterns unexpectedly similar to those produced by the stem and amplifying cells of normal epithelia. From the differing types of colony morphologies formed, it is possible to predict both the growth potential of their constituent cells and their patterns of macromolecular expression. Maintenance of a subpopulation of stem cells during passage of cell lines indicates that the key stem cell property of asymmetrical division persists but is shifted towards enhanced stem cell self-renewal. The presence of malignant epithelial stem cells in vivo has been shown by serial transplantation of primary cancer cells and the present observations indicate that stem cell patterns are robust and persist even in cell lines. An understanding of this behavior should facilitate studies directed towards the molecular or pharmacologic manipulation of malignant stem cell survival.