The commonality of plasticity underlying multipotent tumor cells and embryonic stem cells
The commonality of plasticity underlying multipotent tumor cells and embryonic stem cells
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DOI：
10.1002/jcb.21227
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发表时间：
2007-07-01
影响因子：
4
通讯作者：
Hendrix, Mary J. C.
中科院分区：
文献类型：
--
作者：
Postovit, Lynne-Marie;Costa, Fabricio F.;Hendrix, Mary J. C.
侵袭性癌细胞和多能干细胞在自我更新、增殖和可塑性方面的能力趋同。最近的研究利用了这些相似性，证明肿瘤是由特定的癌症干细胞群产生的，这些干细胞群以一种让人想起正常干细胞的方式，能够自我更新并产生异质性肿瘤群。侵袭性癌细胞的这种干细胞样功能可能归因于胚胎因子如结和癌睾丸特异性抗原（CTA）的异位表达，其通过促进多能性和永生性来保持功能可塑性。在发育过程中，这些胚胎因子的表达受到一系列动态介质的严格调控，包括Lefty等抑制剂的时空表达以及基因组的表观遗传调节。在侵袭性癌细胞中，特别是黑色素瘤，这种调节介质的平衡被破坏，导致多能性相关基因的异常表达。通过将侵袭性癌细胞暴露于胚胎微环境，这种调节介质的平衡得以恢复，从而将肿瘤细胞重编程为更良性的表型。这些严厉的细胞衍生介质，以及它们调节的基因，提供了旨在特异性分化和根除侵袭性癌症的治疗靶点。
Aggressive cancer cells and pluripotent stem cells converge in their capacity for self-renewal, proliferation and plasticity. Recent studies have capitalized on these similarities by demonstrating that tumors arise from specific cancer stem cell populations that, in a manner reminiscent of normal stem cells, are able to both self-renew and give rise to a heterogeneous tumor population. This stem cell like function of aggressive cancer cells is likely attributable to the ectopic expression of embryonic factors such as Nodal and Cancer Testis Specific Antigens (CTAs), which maintain a functional plasticity by promoting pluripotency and immortality. During development, the expression of these embryonic factors is tightly regulated by a dynamic array of mediators, including the spatial and temporal expression of inhibitors such as Lefty, and the epigenetic modulation of the genome. In aggressive cancer cells, particularly melanoma, this balance of regulatory mediators is disrupted, leading to the aberrant expression of pluripotency-associated genes. By exposing aggressive cancer cells to embryonic microenvironments, this balance of regulatory mediators is restored, thereby reprogramming tumor cells to a more benign phenotype. These stern cell-derived mediators, as well as the genes they regulate, provide therapeutic targets designed to specifically differentiate and eradicate aggressive cancers.