Department of Molecular Carcinogenesis, the University of Texas M.D. Anderson Cancer Center, Science Park, 1808 Park Rd. 1C, Smithville, TX 78957, USA.
Cell Res. 2012 Mar;22(3):457-72. doi: 10.1038/cr.2012.13. Epub 2012 Jan 17.
Heterogeneity is an omnipresent feature of mammalian cells in vitro and in vivo. It has been recently realized that even mouse and human embryonic stem cells under the best culture conditions are heterogeneous containing pluripotent as well as partially committed cells. Somatic stem cells in adult organs are also heterogeneous, containing many subpopulations of self-renewing cells with distinct regenerative capacity. The differentiated progeny of adult stem cells also retain significant developmental plasticity that can be induced by a wide variety of experimental approaches. Like normal stem cells, recent data suggest that cancer stem cells (CSCs) similarly display significant phenotypic and functional heterogeneity, and that the CSC progeny can manifest diverse plasticity. Here, I discuss CSC heterogeneity and plasticity in the context of tumor development and progression, and by comparing with normal stem cell development. Appreciation of cancer cell plasticity entails a revision to the earlier concept that only the tumorigenic subset in the tumor needs to be targeted. By understanding the interrelationship between CSCs and their differentiated progeny, we can hope to develop better therapeutic regimens that can prevent the emergence of tumor cell variants that are able to found a new tumor and distant metastases.
异质性是哺乳动物细胞在体外和体内普遍存在的特征。最近人们意识到，即使是在最佳培养条件下的小鼠和人类胚胎干细胞也存在异质性，其中包含多能性以及部分定向分化的细胞。成年器官中的体干细胞也是异质性的，包含许多具有不同再生能力的自我更新细胞的亚群。成年干细胞的分化后代也保留着显著的发育可塑性，这种可塑性可以通过多种实验方法来诱导。与正常干细胞类似，最近的数据表明，癌症干细胞（CSC）也表现出显著的表型和功能异质性，而且 CSC 的后代可以表现出多种可塑性。在这里，我将讨论 CSC 异质性和可塑性在肿瘤发生和发展中的情况，并通过与正常干细胞发育进行比较。认识到癌细胞的可塑性需要对早期的概念进行修正，即只有肿瘤中的肿瘤发生亚群需要被靶向。通过了解 CSC 与其分化后代之间的相互关系，我们可以希望开发出更好的治疗方案，以防止出现能够形成新肿瘤和远处转移的肿瘤细胞变体。
