Epithelial-mesenchymal plasticity of breast cancer stem cells: implications for metastasis and therapeutic resistance.
Epithelial-mesenchymal plasticity of breast cancer stem cells: implications for metastasis and therapeutic resistance.
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DOI：
10.2174/1381612821666141211120604
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发表时间：
2015
影响因子：
3.1
通讯作者：
Wicha MS
中科院分区：
文献类型：
--
作者：
Luo M;Brooks M;Wicha MS
在过去的几十年里，传统的癌症是一个快速增殖的恶性细胞的同质块的观点正在被一个日益复杂的模型所取代，该模型指出癌症是由多种细胞类型组成的复杂组织。多种多样的免疫细胞和其他宿主细胞构成了肿瘤微环境，其支持肿瘤的生长和进展，其中个体癌细胞随着表型和遗传异质性的增加而进化。此外，还变得清楚的是，除了这种细胞和遗传异质性之外，大多数肿瘤表现出由显示不同谱系标志物的肿瘤细胞组成的分层组织，并且在该分层的顶点是能够自我更新的细胞。这些“癌症干细胞”不仅驱动肿瘤生长，还介导转移并导致治疗抵抗。除了显示出显著的遗传和表型异质性外，癌症干细胞在肿瘤微环境调节的过程中保持在间充质样（EMT）和上皮样（MET）状态之间转变的可塑性。这些干细胞状态转换可能在肿瘤转移过程中发挥重要作用。在这篇综述中，我们将讨论有关癌症干细胞可塑性的新知识以及这种可塑性在肿瘤转移中所起的作用。我们还讨论了这些发现对癌症干细胞靶向治疗的发展的影响。
Over the past several decades the traditional view of cancer being a homogeneous mass of rapid proliferating malignant cells is being replaced by a model of ever increasing complexity, which points out that cancers are complex tissues composed of multiple cell types. A large variety of immune and other host cells constitute the tumor microenvironment, which supports the growth and progression of the tumor where individual cancer cells evolve with increasing phenotypic and genetic heterogeneity. Furthermore, it has also become clear that, in addition to this cellular and genetic heterogeneity, most tumors exhibit a hierarchical organization composed of tumor cells displaying divergent lineage markers and at the apex of this hierarchy are cells capable of self-renewal. These “cancer stem cells” not only drive tumor growth, but also mediate metastasis and contribute to treatment resistance. Besides displaying remarkable genetic and phenotypic heterogeneity, cancer stem cells maintain plasticity to transition between mesenchymal-like (EMT) and epithelial-like (MET) states in a process regulated by the tumor microenvironment. These stem cell state transitions may play a fundamental role in the process of tumor metastasis. In this review, we will discuss emerging knowledge regarding the plasticity of cancer stem cells and the role that this plasticity plays in tumor metastasis. We also discuss the implications of these findings for the development of cancer stem cell targeted therapeutics.
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