Elastic free energy drives the shape of prevascular solid tumors.
Elastic free energy drives the shape of prevascular solid tumors.
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DOI：
10.1371/journal.pone.0103245
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Garikipati K
中科院分区：
文献类型：
--
作者：
Mills KL;Kemkemer R;Rudraraju S;Garikipati K
众所周知，机械环境影响健康和疾病中的细胞功能。在这里，我们解决了机械环境如何影响肿瘤生长，特别是实体瘤的形状。在一个体外肿瘤模型中，它隔离了癌症肿瘤细胞和水凝胶之间的机械相互作用，我们发现肿瘤生长为椭圆体，类似于体内肿瘤的相同的，经常报道的观察。具体地，当肿瘤在比肿瘤更硬的水凝胶中生长时，会稳健地出现扁椭圆形肿瘤形状，但是当它们在更柔顺的水凝胶中生长时，它们在形状上保持更接近球形。使用大规模的，非线性弹性计算，我们表明，扁椭圆形的形状最大限度地减少了肿瘤-水凝胶系统的弹性自由能。在消除了一些其他的候选解释，我们假设，弹性自由能的最小化是实验观察到的椭球形的优势的原因。这一结果可能对解释体内早期实体瘤的形状进展具有重要意义，并且是理解实体瘤生长过程的重要一步。
It is well established that the mechanical environment influences cell functions in health and disease. Here, we address how the mechanical environment influences tumor growth, in particular, the shape of solid tumors. In an in vitro tumor model, which isolates mechanical interactions between cancer tumor cells and a hydrogel, we find that tumors grow as ellipsoids, resembling the same, oft-reported observation of in vivo tumors. Specifically, an oblate ellipsoidal tumor shape robustly occurs when the tumors grow in hydrogels that are stiffer than the tumors, but when they grow in more compliant hydrogels they remain closer to spherical in shape. Using large scale, nonlinear elasticity computations we show that the oblate ellipsoidal shape minimizes the elastic free energy of the tumor-hydrogel system. Having eliminated a number of other candidate explanations, we hypothesize that minimization of the elastic free energy is the reason for predominance of the experimentally observed ellipsoidal shape. This result may hold significance for explaining the shape progression of early solid tumors in vivo and is an important step in understanding the processes underlying solid tumor growth.
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