Paradoxical Dependencies of Tumor Dormancy and Progression on Basic Cell Kinetics
Paradoxical Dependencies of Tumor Dormancy and Progression on Basic Cell Kinetics
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DOI：
10.1158/0008-5472.can-09-2115
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发表时间：
2009-11-15
期刊：
影响因子：
11.2
通讯作者：
Hahnfeldt, Philip
中科院分区：
文献类型：
--
作者：
Enderling, Heiko;Anderson, Alexander R. A.;Hahnfeldt, Philip
即使在肿瘤形成后，它也可以早期进入休眠状态，其特征是平衡的细胞增殖和细胞死亡。对这种平衡的干扰可能会影响癌症风险，因为它们可能导致肿瘤的最终终生临床表现，否则可能会保持无症状。以前，我们表明细胞死亡，增殖和迁移可以在改变这种动态中发挥作用，从而了解它们对肿瘤发展的综合影响至关重要。我们开发了一个基于单个细胞的计算机模型，用于研究癌症干细胞及其非干细胞后代的相互作用，以研究早期肿瘤动力学。肿瘤生长的模拟显示，肿瘤生长的三个基本组成部分细胞增殖、迁移和死亡以意想不到的方式结合在一起，控制肿瘤进展，从而控制临床癌症风险。我们发现，非干细胞肿瘤细胞增殖能力的增加和有限的细胞迁移总体上导致抑制增殖和肿瘤生长的空间限制。相比之下，增加细胞死亡率在短期内产生预期的肿瘤尺寸减小，但由于癌症干细胞的释放和自身转移的形成，最终导致矛盾的加速长期生长。[Cancer Res 2009;69（22）：8814-21]
Even after a tumor is established, it can early on enter a state of dormancy marked by balanced cell proliferation and cell death. Disturbances to this equilibrium may affect cancer risk, as they may cause the eventual lifetime clinical presentation of a tumor that might otherwise have remained asymptomatic. Previously, we showed that cell death, proliferation, and migration can play a role in shifting this dynamic, making the understanding of their combined influence on tumor development essential. We developed an individual cell-based computer model of the interaction of cancer stem cells and their nonstem progeny to study early tumor dynamics. Simulations of tumor growth show that three basic components of tumor growth-cell proliferation, migration, and death-combine in unexpected ways to control tumor progression and, thus, clinical cancer risk. We show that increased proliferation capacity in nonstem tumor cells and limited cell migration overall lead to space constraints that inhibit proliferation and tumor growth. By contrast, increasing the rate of cell death produces the expected tumor size reduction in the short term, but results ultimately in paradoxical accelerated long-term growth owing to the liberation of cancer stem cells and formation of self-metastases. [Cancer Res 2009;69(22):8814-21]