Marchant Ben P, Norbury John, Byrne Helen M
Rothamsted Research, Harpenden, Hertfordshire AL5 2JQ, UK.
Math Med Biol. 2006 Sep;23(3):173-96. doi: 10.1093/imammb/dql007. Epub 2006 Apr 20.
Invasion is an important facet of malignant growth that enables tumour cells to colonise adjacent regions of normal tissue. Factors known to influence such invasion include the rate at which the tumour cells produce tissue-degrading molecules, or proteases, and the composition of the surrounding tissue matrix. A common feature of experimental studies is the biphasic dependence of the speed at which the tumour cells invade on properties such as protease production rates and the density of the normal tissue. For example, tumour cells may invade dense tissues at the same speed as they invade less dense tissue, with maximal invasion seen for intermediate tissue densities. In this paper, a theoretical model of malignant invasion is developed. The model consists of two coupled partial differential equations describing the behaviour of the tumour cells and the surrounding normal tissue. Numerical methods show that the model exhibits steady travelling wave solutions that are stable and may be smooth or discontinuous. Attention focuses on the more biologically relevant, discontinuous solutions which are characterised by a jump in the tumour cell concentration. The model also reproduces the biphasic dependence of the tumour cell invasion speed on the density of the surrounding normal tissue. We explain how this arises by seeking constant-form travelling wave solutions and applying non-standard phase plane methods to the resulting system of ordinary differential equations. In the phase plane, the system possesses a singular curve. Discontinuous solutions may be constructed by connecting trajectories that pass through particular points on the singular curve and recross it via a shock. For certain parameter values, there are two points at which trajectories may cross the singular curve and, as a result, two distinct discontinuous solutions may arise.
侵袭是恶性生长的一个重要方面,它使肿瘤细胞能够在正常组织的相邻区域定植。已知影响这种侵袭的因素包括肿瘤细胞产生组织降解分子(即蛋白酶)的速率以及周围组织基质的组成。实验研究的一个共同特征是肿瘤细胞侵袭速度对诸如蛋白酶产生速率和正常组织密度等特性的双相依赖性。例如,肿瘤细胞侵袭致密组织的速度可能与侵袭较疏松组织的速度相同,在中等组织密度时侵袭速度最大。本文建立了一个恶性侵袭的理论模型。该模型由两个耦合的偏微分方程组成,描述了肿瘤细胞和周围正常组织的行为。数值方法表明,该模型具有稳定的行波解,这些解可能是光滑的或不连续的。重点关注更具生物学相关性的不连续解,其特征是肿瘤细胞浓度出现跳跃。该模型还再现了肿瘤细胞侵袭速度对周围正常组织密度的双相依赖性。我们通过寻找常形式行波解并将非标准相平面方法应用于所得的常微分方程组来解释这种现象是如何产生的。在相平面中,该系统具有一条奇异曲线。不连续解可以通过连接穿过奇异曲线上特定点并通过激波重新穿过它的轨迹来构建。对于某些参数值,有两个点轨迹可能穿过奇异曲线,结果可能会出现两个不同的不连续解。