Department of Computer Science, Kroto Institute, North Campus, Broad Lane, University of Sheffield, Sheffield S3 7HQ, UK.
J Theor Biol. 2010 Feb 7;262(3):425-40. doi: 10.1016/j.jtbi.2009.10.002. Epub 2009 Oct 21.
The characteristics of biological tissues are determined by the interactions of large numbers of autonomous cells. These interactions can be mediated remotely by diffusive biochemical factors, or by direct cell-cell contact. E-cadherin is a protein expressed on the surface of normal epithelial cells that plays a key role in mediating intercellular adhesion via calcium-dependent homotypic interactions. E-cadherin is a metastasis-suppressor protein and its loss of function is associated with malignant progression. The purpose of this study was to apply an agent-based simulation paradigm in order to examine the emergent growth properties of mixed populations consisting of normal and E-cadherin defective cells in monolayer cell culture. Specifically, we have investigated the dynamics of normal cell:cell interactions in terms of intercellular adhesion and migration, and have used a simplified rule to represent the concepts of juxtacrine epidermal growth factor receptor (EGFR) activation and subsequent effect on cell proliferation. This cellular level control determines the overall population growth in a simulated experiment. Our approach provides a tool for modelling the development of defined biological abnormalities in epithelial and other biological tissues, raising novel predictions for future experimental testing. The results predict that even a relatively small number of abnormal ('anti-social') cells can modify the rate of the total population expansion, but the magnitude of this effect also depends on the extrinsic (culture) environment. In addition to directly influencing population dynamics, 'anti-social' cells can also disrupt the behaviour of the normal cells around them.
生物组织的特性取决于大量自主细胞的相互作用。这些相互作用可以通过扩散的生化因子远程介导，也可以通过直接的细胞间接触介导。E-钙黏蛋白是一种在正常上皮细胞表面表达的蛋白质，通过钙依赖性同种型相互作用在介导细胞间黏附中起着关键作用。E-钙黏蛋白是一种转移抑制蛋白，其功能丧失与恶性进展有关。本研究旨在应用基于代理的模拟范例，以检查单层细胞培养中正常和 E-钙黏蛋白缺陷细胞混合群体的新兴生长特性。具体来说，我们研究了正常细胞间相互作用的动力学，包括细胞间黏附和迁移，并使用简化规则来表示旁分泌表皮生长因子受体 (EGFR) 激活及其对细胞增殖的后续影响的概念。这种细胞水平的控制决定了模拟实验中的总体群体生长。我们的方法为上皮细胞和其他生物组织中特定生物异常的发展提供了建模工具，为未来的实验测试提出了新的预测。结果表明，即使是相对较少的异常（“反社会”）细胞也可以改变总群体扩张的速度，但这种效应的大小也取决于外在（培养）环境。“反社会”细胞除了直接影响群体动态外，还可以破坏其周围正常细胞的行为。
