Symmetric division of cancer stem cells - a key mechanism in tumor growth that should be targeted in future therapeutic approaches
Symmetric division of cancer stem cells - a key mechanism in tumor growth that should be targeted in future therapeutic approaches
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DOI：
10.1038/sj.clpt.6100202
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发表时间：
2007-06-01
影响因子：
6.7
通讯作者：
Runquist, O. A.
中科院分区：
文献类型：
--
作者：
Boman, B. M.;Wicha, M. S.;Runquist, O. A.
由于肿瘤干细胞(SCs)驱动肿瘤生长，只有通过清除这些癌症干细胞才能获得药物治疗。为了研究开发针对癌症干细胞的药物的方法，我们研究了在结直肠癌(CRC)发展过程中干细胞群体中细胞机制和动力学的变化。我们使用计算机模型来确定哪些变化可能会导致结直肠癌中SC和非SC人口的指数增长。我们的结果表明，唯一可以解释这些亚群如何在结直肠癌发展中呈指数级增长的机制是对称性干细胞分裂的增加。这一发现表明，任何旨在有效治疗结直肠癌和其他癌症的系统疗法都必须控制或消除肿瘤中对称性的癌症SC分裂，同时最小限度地影响非肿瘤组织的正常SC分裂。
As cancer stem cells (SCs) drive tumor growth, it is only through the elimination of those cancer SCs that a pharmacologic cure can be attained. To study ways to develop drugs that target cancer SC, we investigated changes in cellular mechanisms and kinetics that occur in SC populations during colorectal cancer (CRC) development. We used computer modeling to determine which changes could give rise to exponential increases in both SC and non-SC populations in CRC. Our results show that the only mechanism that can explain how these subpopulations increase exponentially in CRC development involves an increase in symmetric SC cell division. This finding suggests that any systemic therapies designed to effectively treat CRC and other cancers must act to control or eliminate symmetrical cancer SC division in tumors, while minimally affecting normal SC division in non-tumor tissues.