Acid-mediated tumour cell invasion: a discrete modelling approach using the extended Potts model.
Acid-mediated tumour cell invasion: a discrete modelling approach using the extended Potts model.
复制标题
酸介导的肿瘤细胞侵袭：使用扩展 Potts 模型的离散建模方法。
DOI：
10.1007/s10585-013-9579-4
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发表时间：
2013
影响因子：
4
通讯作者：
Al-Husari M
中科院分区：
文献类型：
--
作者：
Al-Husari M
酸性细胞外pH已被证明在一些肿瘤的侵袭和转移级联过程中起着关键作用。在这项研究中，我们研究了细胞外酸度对肿瘤侵袭聚焦的影响，特别是对细胞黏附、蛋白水解酶活性和细胞增殖的影响。我们使用细胞Potts模型进行的数值模拟表明，在酸性细胞外pH下，细胞-基质黏附强度的变化对肿瘤侵袭力的影响与蛋白水解酶活性的增加具有相似的影响。我们还发现，在生理pH下培养的肿瘤细胞往往较大，并且与在酸性pH下培养的肿瘤相比，肿瘤发展成“弥漫”的形态，后者在前进的前沿显示出突出的“手指”。一个关键的模型预测是观察到，在低细胞外pH条件下培养细胞对侵袭的主要影响来自于细胞间和细胞基质黏附强度以及蛋白水解酶分泌速率的变化。然而，我们表明，蛋白分解的影响需要是显著的，因为低到中等的变化只对细胞侵袭性有名义上的影响。我们发现，低pHe值对细胞大小和增殖率的影响对细胞侵袭力的影响要小得多。
Acidic extracellular pH has been shown to play a crucial part in the invasive and metastatic cascade of some tumours. In this study, we examine the effect of extracellular acidity on tumour invasion focusing, in particular, on cellular adhesion, proteolytic enzyme activity and cellular proliferation. Our numerical simulations using a cellular Potts model show that, under acidic extracellular pH, changes in cell–matrix adhesion strength has a comparable effect on tumour invasiveness as the increase in proteolytic enzyme activity. We also show that tumour cells cultured under physiological pH tend to be large and the tumours develop a "diffuse" morphology compared to those cultured at acidic pH, which display protruding "fingers" at the advancing front. A key model prediction is the observation that the main effect on invasion from culturing cells at low extracellular pH stems from changes in the intercellular and cell–matrix adhesion strengths and proteolytic enzyme secretion rate. However, we show that the effects of proteolysis needs to be significant as low to moderate changes only has nominal effects on cell invasiveness. We find that the low pHeeffects on cell size and proliferation rate have much lower influence on cell invasiveness.