真实多细胞肿瘤球体模型中肿瘤微环境的涌现特性
Emergent Properties of Tumor Microenvironment in a Real-life Model of Multicell Tumor Spheroids
摘要：
多细胞肿瘤球状体是实体肿瘤血管形成前阶段的重要{ \it in vitro}模型，其大小远低于诊断极限：因此球状体的生物物理模型能够阐明肿瘤在其发展的关键阶段的内部运作和组织。为此，我们开发了一个计算机程序，它整合了单个细胞的行为及其与其他细胞和周围环境的相互作用。它基于对单个肿瘤细胞的代谢、生长、增殖和死亡的定量描述，以及对生物化学和机械细胞-细胞和细胞-环境相互作用进行建模的方程。该程序再现了现有的实验数据的球体，并产生独特的看法，他们的微环境。模拟显示了营养物质、代谢物和细胞的复杂内部流动和运动，这些是目前实验技术无法观察到的，并为肿瘤发展提供了新的线索，为未来的治疗提供了强有力的提示。
英文摘要：
Multicellular tumor spheroids are an important {\it in vitro} model of the pre-vascular phase of solid tumors, for sizes well below the diagnostic limit: therefore a biophysical model of spheroids has the ability to shed light on the internal workings and organization of tumors at a critical phase of their development. To this end, we have developed a computer program that integrates the behavior of individual cells and their interactions with other cells and the surrounding environment. It is based on a quantitative description of metabolism, growth, proliferation and death of single tumor cells, and on equations that model biochemical and mechanical cell-cell and cell-environment interactions. The program reproduces existing experimental data on spheroids, and yields unique views of their microenvironment. Simulations show complex internal flows and motions of nutrients, metabolites and cells, that are otherwise unobservable with current experimental techniques, and give novel clues on tumor development and strong hints for future therapies.
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