Migration rules: tumours are conglomerates of self-metastases
Migration rules: tumours are conglomerates of self-metastases
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DOI：
10.1038/sj.bjc.6605071
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发表时间：
2009-06-09
影响因子：
8.8
通讯作者：
Hahnfeldt, P.
中科院分区：
文献类型：
--
作者：
Enderling, H.;Hlatky, L.;Hahnfeldt, P.
肿瘤是由不同细胞类型组成的异质群体：具有自我更新能力的干细胞和缺乏这种能力的分化程度较高的细胞。正在发育的肿瘤的总体生长行为很大程度上取决于这些细胞的组合动力学相互作用。通过使用基于试剂的计算机方法跟踪单个癌细胞的命运，我们应用细胞增殖、迁移和细胞死亡的基本规则来显示这些动力学参数如何相互作用以进行控制，并可能决定定义肿瘤发展中的空间和时间肿瘤生长动力学。当迁移率较小时，由于后代的寿命有限和空间限制，单个癌症干细胞只能产生小的、自限性的克隆。相比之下，高迁移率可能会打破这种平衡，在旧克隆之外的位置播种新的克隆。就这样，肿瘤不断地“自我转移”。与直觉相反，当增殖能力低且细胞死亡率高时，由于释放了自我转移扩张的空间，肿瘤生长加速。增殖和细胞死亡的变化增加了细胞迁移的速度，有利于整个肿瘤的生长。迁移对肿瘤生长的主要影响导致肿瘤生长对增殖能力和细胞死亡的意外依赖性。这些依赖性将为标准治疗方法提供信息，这些方法预计对细胞杀伤和有丝分裂停滞产生积极反应。英国癌症杂志 (2009) 100, 1917-1925。 doi: 10.1038/sj.bjc.6605071 www.bjcancer.com 在线发布 2009 年 5 月 19 日 (C) 2009 英国癌症研究中心
Tumours are heterogeneous populations composed of different cells types: stem cells with the capacity for self-renewal and more differentiated cells lacking such ability. The overall growth behaviour of a developing neoplasm is determined largely by the combined kinetic interactions of these cells. By tracking the fate of individual cancer cells using agent-based methods in silico, we apply basic rules for cell proliferation, migration and cell death to show how these kinetic parameters interact to control, and perhaps dictate defining spatial and temporal tumour growth dynamics in tumour development. When the migration rate is small, a single cancer stem cell can only generate a small, self-limited clone because of the finite life span of progeny and spatial constraints. By contrast, a high migration rate can break this equilibrium, seeding new clones at sites outside the expanse of older clones. In this manner, the tumour continually 'self-metastasises'. Counterintuitively, when the proliferation capacity is low and the rate of cell death is high, tumour growth is accelerated because of the freeing up of space for self-metastatic expansion. Changes to proliferation and cell death that increase the rate at which cells migrate benefit tumour growth as a whole. The dominating influence of migration on tumour growth leads to unexpected dependencies of tumour growth on proliferation capacity and cell death. These dependencies stand to inform standard therapeutic approaches, which anticipate a positive response to cell killing and mitotic arrest. British Journal of Cancer (2009) 100, 1917-1925. doi: 10.1038/sj.bjc.6605071 www.bjcancer.com Published online 19 May 2009 (C) 2009 Cancer Research UK