Department of Systems Biology, Center of Molecular Immunology, La Habana, Cuba.
Soft and Living Matter Lab, Istituto di Nanotecnologia (CNR-NANOTEC), Rome, Italy.
Sci Rep. 2017 Jun 8;7(1):3103. doi: 10.1038/s41598-017-03342-3.
We introduce an in silico model for the initial spread of an aberrant phenotype with Warburg-like overflow metabolism within a healthy homeostatic tissue in contact with a nutrient reservoir (the blood), aimed at characterizing the role of the microenvironment for aberrant growth. Accounting for cellular metabolic activity, competition for nutrients, spatial diffusion and their feedbacks on aberrant replication and death rates, we obtain a phase portrait where distinct asymptotic whole-tissue states are found upon varying the tissue-blood turnover rate and the level of blood-borne primary nutrient. Over a broad range of parameters, the spreading dynamics is bistable as random fluctuations can impact the final state of the tissue. Such a behaviour turns out to be linked to the re-cycling of overflow products by non-aberrant cells. Quantitative insight on the overall emerging picture is provided by a spatially homogeneous version of the model.
我们引入了一个计算模型，用于模拟在与营养库（如血液）接触的健康稳态组织内，异常表型的初始扩散，该异常表型具有类似于瓦博格效应的代谢溢出。该模型旨在描述微环境对异常生长的作用。通过考虑细胞代谢活性、对营养物质的竞争、空间扩散以及它们对异常复制和死亡率的反馈，我们得到了一个相图，其中在改变组织与血液的周转率以及血液中主要营养素的水平时，可以发现不同的整体组织状态的渐近解。在广泛的参数范围内，扩散动力学是双稳态的，因为随机波动会影响组织的最终状态。这种行为与非异常细胞对溢出产物的再循环有关。通过模型的空间均匀化版本，提供了对整体出现的情况的定量见解。
