Essential operating principles for tumor spheroid growth.
Essential operating principles for tumor spheroid growth.
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DOI：
10.1186/1752-0509-2-110
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发表时间：
2008-12-23
影响因子：
--
通讯作者：
Hunt CA
中科院分区：
文献类型：
--
作者：
Engelberg JA;Ropella GE;Hunt CA
我们的目标是在计算机中发现EMT6/Ro小鼠乳腺肿瘤球体培养过程中实现的工作原理的合理表述。为了达到这一目标，我们设计并反复伪造了一种基于代理的EMT6球体生长模拟物。EMT6球体表现出一致和可预测的生长特征，这意味着单个细胞的行为受到严格的控制和调节。理解单个细胞行为如何影响系统行为的一种方法是发现一组原则，这些原则使抽象的智能体仅使用智能体直接环境中可用的信息就能表现出相似的行为。我们列出了EMT6球体生长的关键属性，这成为我们的行为目标。包括被静止和增殖细胞包围的坏死核心的发育，以及两种不同营养水平的生长数据。然后，我们创建了一个由准自主软件代理和一个抽象环境组成的模拟物，让它们可以在其中操作。该系统被设计成在执行时可以模拟EMT6细胞在培养中形成球体。每个代理使用一套相同的公理操作原则。按照顺序，我们使用目标属性列表来证伪和修改这些公理，直到模拟物显示的行为和属性在预定的目标范围内，从而达到一定程度的验证。最终的模拟需要九个公理。我们假设，经过验证的类似物的工作原理是EMT6/Ro细胞在肿瘤球体发育过程中所利用的原理的合理代表。
Our objective was to discover in silico axioms that are plausible representations of the operating principles realized during characteristic growth of EMT6/Ro mouse mammary tumor spheroids in culture. To reach that objective we engineered and iteratively falsified an agent-based analogue of EMT6 spheroid growth. EMT6 spheroids display consistent and predictable growth characteristics, implying that individual cell behaviors are tightly controlled and regulated. An approach to understanding how individual cell behaviors contribute to system behaviors is to discover a set of principles that enable abstract agents to exhibit closely analogous behaviors using only information available in an agent's immediate environment. We listed key attributes of EMT6 spheroid growth, which became our behavioral targets. Included were the development of a necrotic core surrounded by quiescent and proliferating cells, and growth data at two distinct levels of nutrient. We then created an analogue made up of quasi-autonomous software agents and an abstract environment in which they could operate. The system was designed so that upon execution it could mimic EMT6 cells forming spheroids in culture. Each agent used an identical set of axiomatic operating principles. In sequence, we used the list of targeted attributes to falsify and revise these axioms, until the analogue exhibited behaviors and attributes that were within prespecified ranges of those targeted, thereby achieving a level of validation. The finalized analogue required nine axioms. We posit that the validated analogue's operating principles are reasonable representations of those utilized by EMT6/Ro cells during tumor spheroid development.
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