Alarcón T, Byrne H M, Maini P K
Centre for Mathematical Biology, Mathematical Institute, University of Oxford, 24-29 St Giles', Oxford OX1 3LB, UK.
J Theor Biol. 2003 Nov 21;225(2):257-74. doi: 10.1016/s0022-5193(03)00244-3.
Most of the existing mathematical models for tumour growth and tumour-induced angiogenesis neglect blood flow. This is an important factor on which both nutrient and metabolite supply depend. In this paper we aim to address this shortcoming by developing a mathematical model which shows how blood flow and red blood cell heterogeneity influence the growth of systems of normal and cancerous cells. The model is developed in two stages. First we determine the distribution of oxygen in a native vascular network, incorporating into our model features of blood flow and vascular dynamics such as structural adaptation, complex rheology and red blood cell circulation. Once we have calculated the oxygen distribution, we then study the dynamics of a colony of normal and cancerous cells, placed in such a heterogeneous environment. During this second stage, we assume that the vascular network does not evolve and is independent of the dynamics of the surrounding tissue. The cells are considered as elements of a cellular automaton, whose evolution rules are inspired by the different behaviour of normal and cancer cells. Our aim is to show that blood flow and red blood cell heterogeneity play major roles in the development of such colonies, even when the red blood cells are flowing through the vasculature of normal, healthy tissue.
现有的大多数肿瘤生长和肿瘤诱导血管生成的数学模型都忽略了血流。而血流是营养物质和代谢产物供应所依赖的一个重要因素。在本文中,我们旨在通过建立一个数学模型来解决这一缺陷,该模型展示了血流和红细胞异质性如何影响正常细胞和癌细胞系统的生长。该模型分两个阶段构建。首先,我们确定天然血管网络中的氧气分布,将血流和血管动力学特征(如结构适应性、复杂流变学和红细胞循环)纳入我们的模型。一旦我们计算出氧气分布,然后我们研究置于这种异质环境中的正常细胞和癌细胞群体的动力学。在第二阶段,我们假设血管网络不发生演化且独立于周围组织的动力学。细胞被视为细胞自动机的元素,其演化规则受正常细胞和癌细胞不同行为的启发。我们的目的是表明,即使红细胞在正常健康组织的脉管系统中流动,血流和红细胞异质性在这种细胞群体的发展中也起着主要作用。