Cancer stem cells and tumor transdifferentiation: implications for novel therapeutic strategies.
Cancer stem cells and tumor transdifferentiation: implications for novel therapeutic strategies.
复制标题
DOI：
--
复制
发表时间：
2013-03
影响因子：
1.8
通讯作者：
M. T. Shekhani;A. Jayanthy;Nityanand Maddodi;V. Setaluri
中科院分区：
文献类型：
--
作者：
M. T. Shekhani;A. Jayanthy;Nityanand Maddodi;V. Setaluri
高度恶性肿瘤大多由快速增殖的细胞组成。然而，肿瘤也含有一些处于静止状态的细胞，其特征在于慢循环，表达干细胞标志物并具有引发新肿瘤的能力。这些静止的细胞，现在通常被称为“癌症干细胞”（CSC）（或“癌症起始细胞”），能够再生整个肿瘤-因为它发生在转移扩散中。干细胞样细胞引发肿瘤的过程可能涉及静止CSC分化为快速增殖的肿瘤细胞。肿瘤中存在缓慢循环、静止的干细胞样细胞及其引发肿瘤的能力的重要意义在于，它们有助于对针对杀死快速分裂细胞的常规化疗和放疗的治疗产生抗性。然而，与正常干细胞类似，CSC也可以潜在地转分化成不同于肿瘤产生的原始谱系的细胞谱系。因此，CSC的转分化提供了一种可能的治疗策略，但尚未得到充分利用。在这篇文章中，我们提供了一个全面的审查的概念，在肿瘤细胞转分化，并讨论了转分化的机制，强调其相关的潜在的新的治疗策略。
Highly malignant tumors mostly consist of rapidly proliferating cells. However, tumors also contain a few cells in a quiescent state that can be characterized as slow-cycling, expressing markers of stem cells and possessing the ability to initiate new tumors. These quiescent cells, now generally termed 'cancer stem cells' (CSC) (or 'cancer initiating cells'), are capable of regenerating the entire tumor--as it occurs in metastatic spread. This process of tumor initiation by stem-like cells presumably involves differentiation of quiescent CSC into rapidly proliferating tumor cells. An important implication of the presence of slow cycling, quiescent stem-like cells in the tumor and their ability to initiate tumors is that they contribute to the resistance to treatments by conventional chemo- and radiotherapy directed toward killing rapidly dividing cells. However, similar to normal stem cells, the CSC could also potentially transdifferentiate into cell lineages other than the original lineage from which the tumor arose. Therefore, transdifferentiation of CSC offers a possible therapeutic strategy which has not yet been fully exploited. In this article, we provide a comprehensive review of the concepts in tumor cell transdifferentiation and discuss the mechanisms of transdifferentiation with emphasis on their relevance to potential novel treatment strategies.