Computational Intelligence Group, Faculty of Engineering and Environment, University of Northumbria at Newcastle, UK.
Department of Applied Sciences, Faculty of Health and Life Sciences, University of Northumbria at Newcastle, UK.
J Theor Biol. 2013 Nov 21;337:150-60. doi: 10.1016/j.jtbi.2013.08.016. Epub 2013 Aug 27.
Cancer metastasis is a complex multistep process which allows cancer cells to establish new tumours in distant organs. The process of metastasis involves cell migration and invasion; it is what makes cancer a fatal disease. The efficiency of most cancer treatments depends on metastasis suppression. Maspin is a type II tumour metastasis suppressor which has multiple cellular effects. It has been described as a key regulatory protein in both the intracellular and extracellular environments. Maspin has been shown to reduce cell migration, invasion, proliferation and angiogenesis, and increase apoptosis and cell-cell adhesion in in vitro and in vivo experiments. The clinical data regarding the predictive effects of maspin expression are variable. To date, the whole cellular mechanisms that maspin uses to influence tumour cell behaviours have not been clearly defined. The diversity of the effects of maspin motivated us to develop an intelligent model to investigate its effects on cellular proliferation and migration. This paper reports a hybrid model of solid tumour growth in order to investigate the impact of maspin on the growth and evolutionary dynamics of the cancer cell. A feed-forward neural network was used to model the behaviours (proliferation, quiescence, apoptosis and/or movement) of each cell, which has been suggested as a suitable model of cell signalling pathways. Results show that maspin reduces migration by 10-40%, confirmed by published in vitro data. The model also shows a reduction in cell proliferation by 20-30% in the presence of maspin. So far, this is the first attempt to model the effect of maspin in a computational model to verify in vitro data. This will provide new insights into the tumour suppressive properties of maspin and inform the development of novel cancer therapies.
癌症转移是一个复杂的多步骤过程，使癌细胞能够在远处的器官中建立新的肿瘤。转移的过程涉及细胞迁移和侵袭；这就是癌症成为致命疾病的原因。大多数癌症治疗的效果取决于转移抑制。Maspin 是一种 II 型肿瘤转移抑制因子，具有多种细胞效应。它被描述为细胞内和细胞外环境中的关键调节蛋白。Maspin 已被证明可减少细胞迁移、侵袭、增殖和血管生成，并增加体外和体内实验中的细胞凋亡和细胞间粘附。关于 maspin 表达的预测效果的临床数据是可变的。迄今为止，maspin 影响肿瘤细胞行为的整个细胞机制尚未明确界定。Maspin 效应的多样性促使我们开发了一种智能模型来研究其对细胞增殖和迁移的影响。本文报告了一种用于研究 maspin 对肿瘤细胞生长和进化动力学影响的实体肿瘤生长混合模型。前馈神经网络用于模拟每个细胞的行为（增殖、静止、凋亡和/或运动），该模型已被提议作为细胞信号通路的合适模型。结果表明，maspin 通过体外数据证实了迁移减少了 10-40%。该模型还显示了在有 maspin 的情况下细胞增殖减少了 20-30%。到目前为止，这是首次尝试在计算模型中模拟 maspin 的效果以验证体外数据。这将为 maspin 的肿瘤抑制特性提供新的见解，并为新型癌症疗法的开发提供信息。
