Marciniak-Czochra Anna, Kimmel Marek
Institute of Applied Mathematics, University of Heidelberg, Im Neuenheimer Feld 294, 69120 Heidelberg, Germany.
J Theor Biol. 2007 Feb 7;244(3):375-87. doi: 10.1016/j.jtbi.2006.08.021. Epub 2006 Sep 14.
We consider a system composed of a tubular sheet of early tumor cells, occupying the surface of a structure existing in the organism. We assume that the cells have a potential for proliferation in response to a growth factor. This model can be thought of as representing an early stage (pre-in situ) of tumor evolution. A biomedical example of such process might be the atypical adenomatous hyperplasia in the lung. Destabilization of the equilibrium in such system represents initial invasion of cancer. We are looking for a transition from a slightly perturbed equilibrium state to uncontrolled and irregular growth. We examine a mathematical model of a population of cells distributed over a linear or tubular structure. Growth of cells is regulated by a growth factor, which can diffuse over the structure. Aside from this, production of cells and of the growth factor is governed by a pair of ordinary differential equations. Equation for the cell number follows from an accepted model of cell cycle. Equation for the bounded receptor particle number follows from a time-continuous Markov process. We demonstrate existence of the solutions of the complete model, using the method of invariant rectangles. We find conditions under which diffusion causes destabilization of the spatially homogeneous steady state, leading to exponential growth and apparently chaotic spatial patterns, following a period of almost constancy. This phenomenon may serve as a mathematical explanation of "unexpected" rapid growth and invasion of temporarily stable structures composed of cancer cells.
我们考虑一个由早期肿瘤细胞构成的管状薄片组成的系统,该薄片占据生物体中现有结构的表面。我们假设细胞具有响应生长因子而增殖的潜力。这个模型可以被认为是代表肿瘤演化的早期阶段(原位前期)。这种过程的一个生物医学实例可能是肺部的非典型腺瘤样增生。此类系统中平衡的不稳定代表癌症的初始侵袭。我们正在寻找从轻微扰动的平衡状态到不受控制的不规则生长的转变。我们研究分布在线性或管状结构上的细胞群体的数学模型。细胞的生长由一种生长因子调节,该生长因子可在结构上扩散。除此之外,细胞和生长因子的产生由一对常微分方程控制。细胞数量的方程源自公认的细胞周期模型。有界受体粒子数量的方程源自一个时间连续的马尔可夫过程。我们使用不变矩形方法证明了完整模型解的存在性。我们找到了扩散导致空间均匀稳态不稳定的条件,从而在经过一段几乎恒定的时期后导致指数增长和明显的混沌空间模式。这种现象可以作为对由癌细胞组成的暂时稳定结构“意外”快速生长和侵袭的数学解释。