Istituto di Analisi dei Sistemi ed Informatica "A. Ruberti" - CNR, Roma, Italy.
J Theor Biol. 2010 Jan 7;262(1):142-50. doi: 10.1016/j.jtbi.2009.09.024. Epub 2009 Sep 23.
Although commonly related to nutrient deprivation, the cause of the formation of the necrotic core in the multicellular tumour spheroids is still a controversial issue. We propose a simple model for the cell ATP production that assumes glucose and lactate as the only fuel substrates, and describes the main reactions occurring in the glycolytic and the oxidative pathways. Under the key assumption that cell death occurs when ATP production falls to a critical level, we formulate a multiscale model that integrates the energy metabolism at the cellular level with the diffusive transport of the metabolites in the spheroid mass. The model has been tested by predicting the measurements of the necrotic radius obtained by Freyer and Sutherland (1986a) in EMT6/Ro spheroids under different concentrations of glucose and oxygen in the culture medium. The results appear to be in agreement with the hypothesis that necrosis is caused by ATP deficit.
尽管通常与营养缺乏有关，但多细胞肿瘤球体中坏死核心形成的原因仍然存在争议。我们提出了一个简单的细胞 ATP 生成模型，假设葡萄糖和乳酸是唯一的燃料底物，并描述了糖酵解和氧化途径中发生的主要反应。根据细胞死亡发生在 ATP 生成降至临界水平的关键假设，我们制定了一个多尺度模型，将细胞水平的能量代谢与球体质量中代谢物的扩散运输相结合。该模型通过预测 Freyer 和 Sutherland（1986a）在 EMT6/Ro 球体中不同浓度的葡萄糖和氧气培养条件下获得的坏死半径的测量值得到了验证。结果似乎与 ATP 不足导致坏死的假设一致。
