Mathematical Modeling of the Function of Warburg Effect in Tumor Microenvironment.
Mathematical Modeling of the Function of Warburg Effect in Tumor Microenvironment.
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DOI：
10.1038/s41598-018-27303-6
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发表时间：
2018-06-11
影响因子：
4.6
通讯作者：
Sanati-Nezhad A
中科院分区：
文献类型：
--
作者：
Shamsi M;Saghafian M;Dejam M;Sanati-Nezhad A
肿瘤细胞以其增加的葡萄糖摄取率而闻名，即使在充足的氧气存在下。这种代谢向有氧糖酵解的转变被称为Warburg效应。尽管对这一现象的原因和后果进行了大量的研究，但对Warburg效应如何影响肿瘤的生长和进展知之甚少。我们开发了一个多尺度计算模型来探索肿瘤微环境中癌细胞葡萄糖代谢对肿瘤发生行为的详细影响。尽管存在糖酵解性肿瘤，但非糖酵解性肿瘤的生长依赖于一致的形态，而不会明显干扰肿瘤微环境的葡萄糖和酸浓度。葡萄糖代谢的上调有助于在早期肿瘤生长期间将氧水平保持在缺氧极限以上，从而消除了新血管募集的需要。重要的是，模拟肿瘤在葡萄糖摄取速率范围内的生长表明，存在一个葡萄糖摄取速率范围内的肿瘤最具侵袭性，即它可以对其微环境施加最大的酸性胁迫，并最有效地竞争葡萄糖供应。此外，在相同的光谱范围内，肿瘤可以生长到侵袭性形态，而其大小并没有明显缩小。
Tumor cells are known for their increased glucose uptake rates even in the presence of abundant oxygen. This altered metabolic shift towards aerobic glycolysis is known as the Warburg effect. Despite an enormous number of studies conducted on the causes and consequences of this phenomenon, little is known about how the Warburg effect affects tumor growth and progression. We developed a multi-scale computational model to explore the detailed effects of glucose metabolism of cancer cells on tumorigenesis behavior in a tumor microenvironment. Despite glycolytic tumors, the growth of non-glycolytic tumor is dependent on a congruous morphology without markedly interfering with glucose and acid concentrations of the tumor microenvironment. Upregulated glucose metabolism helped to retain oxygen levels above the hypoxic limit during early tumor growth, and thus obviated the need for neo-vasculature recruitment. Importantly, simulating growth of tumors within a range of glucose uptake rates showed that there exists a spectrum of glucose uptake rates within which the tumor is most aggressive, i.e. it can exert maximal acidic stress on its microenvironment and most efficiently compete for glucose supplies. Moreover, within the same spectrum, the tumor could grow to invasive morphologies while its size did not markedly shrink.
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DOI：
10.1073/pnas.1610954113
发表时间：
2016-09-06
影响因子：
11.1
作者：
Hulikova, Alzbeta;Black, Nicholas;Swietach, Pawel
通讯作者：
Swietach, Pawel
影响因子：
11.2
作者：
Curtarello, Matteo;Zulato, Elisabetta;Indraccolo, Stefano
通讯作者：
Indraccolo, Stefano
肿瘤微环境产生的酸度驱动局部侵袭。
影响因子：
11.2
作者：
Estrella V;Chen T;Lloyd M;Wojtkowiak J;Cornnell HH;Ibrahim-Hashim A;Bailey K;Balagurunathan Y;Rothberg JM;Sloane BF;Johnson J;Gatenby RA;Gillies RJ
通讯作者：
Gillies RJ
影响因子：
2.4
作者：
Jang, Se Min;Han, Hulin;Paik, Seung Sam
通讯作者：
Paik, Seung Sam
影响因子：
8.5
作者：
Basanta, D.;Simon, M.;Deutsch, A.
通讯作者：
Deutsch, A.