Computational Science, Faculty of Science, University of Amsterdam, Amsterdam, the Netherlands.
Cancer Res. 2010 Jan 1;70(1):46-56. doi: 10.1158/0008-5472.CAN-09-3663.
The recently developed concept of cancer stem cells (CSC) sheds new light on various aspects of tumor growth and progression. Here, we present a mathematical model of malignancies to investigate how a hierarchical organized cancer cell population affects the fundamental properties of solid malignancies. We establish that tumors modeled in a CSC context more faithfully resemble human malignancies and show invasive behavior, whereas tumors without a CSC hierarchy do not. These findings are corroborated by in vitro studies. In addition, we provide evidence that the CSC model is accompanied by highly altered evolutionary dynamics compared with the ones predicted to exist in a stochastic, nonhierarchical tumor model. Our main findings indicate that the CSC model allows for significantly higher tumor heterogeneity, which may affect therapy resistance. Moreover, we show that therapy which fails to target the CSC population is not only unsuccessful in curing the patient, but also promotes malignant features in the recurring tumor. These include rapid expansion, increased invasion, and enhanced heterogeneity.
最近提出的癌症干细胞 (CSC) 概念为肿瘤生长和进展的各个方面提供了新的视角。在这里，我们构建了一个描述恶性肿瘤的数学模型，用于研究分层组织的癌细胞群体如何影响实体恶性肿瘤的基本特性。我们发现，在 CSC 环境下建模的肿瘤更能真实地模拟人类恶性肿瘤，并表现出侵袭性行为，而没有 CSC 层次结构的肿瘤则不会。这些发现得到了体外研究的证实。此外，我们提供的证据表明，与预测存在于随机、非分层肿瘤模型中的进化动力学相比，CSC 模型的进化动力学发生了高度改变。我们的主要发现表明，CSC 模型允许更高的肿瘤异质性，这可能会影响治疗效果。此外，我们还表明，未能针对 CSC 群体进行治疗不仅不能成功治愈患者，而且还会促进复发性肿瘤中的恶性特征，包括快速增殖、侵袭性增强和异质性增加。
