A mathematical model for progression and heterogeneity in colorectal cancer dynamics
A mathematical model for progression and heterogeneity in colorectal cancer dynamics
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DOI：
10.1016/j.tpb.2011.01.001
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发表时间：
2011-06-01
影响因子：
1.4
通讯作者：
Lorenzi, Tommaso
中科院分区：
文献类型：
--
作者：
Delitala, Marcello;Lorenzi, Tommaso
本文论述了一个数学模型的发展，描述癌症动力学在细胞的scale.The选定的案例研究关注的结肠癌和直肠癌，这起源于结肠直肠隐窝。细胞内的隐窝被假定为组织根据一个隔室样的安排，并均匀混合。本文提出了一个癌症发展的数学模型。该模型描述了在单个隐窝中不同发育阶段的多个克隆细胞亚群的产生，并进行了渐近分析和模拟。所获得的结果提供了一些见解突变，增殖和分化现象对癌症动力学所发挥的作用。特别是，获得额外的生长能力和细胞分化的减少似乎更可能是致癌作用背后的驱动力，而不是突变率的增加。相反，突变率似乎影响进展动力学和肿瘤内异质性。细胞在不同分化阶段在结直肠癌的发生和发展中所起的作用得到了强调。这些结果支持了干细胞在癌症发展中起关键作用的事实，以及transit-amplifying细胞也可以在致癌作用中发挥积极作用的想法。(C)2011 Elsevier Inc. All rights reserved.
This paper deals with the development of a mathematical model that describes cancer dynamics at the cellular scale.The selected case study concerns colon and rectum cancer, which originates in colorectal crypts. Cells inside the crypts are assumed to be organized according to a compartmental-like arrangement and to be homogeneously mixing. A mathematical model for cancer progression is proposed here. This model describes the generation of multiple clonal sub-populations of cells at different progression stages in a single crypt.Asymptotic analysis and simulations are developed with an exploratory aim. The obtained results offer some insights into the role played by mutation, proliferation and differentiation phenomena on cancer dynamics. In particular, the acquisition of an additional growing power and a reduction for cellular differentiation seem more likely to be the driving force behind carcinogenesis rather than an increase in the mutation rate. The mutation rate instead seems to affect progression dynamics and intra-tumor heterogeneity. The role played by cells, at different differentiation stages, in the onset and progression of colorectal cancer is highlighted. The results support the fact that stem cells play a key role in cancer development and the idea that transit-amplifying cells could also take on an active role in carcinogenesis. (C) 2011 Elsevier Inc. All rights reserved.