Solid stress generated by spheroid growth estimated using a linear poroelasticity model
Solid stress generated by spheroid growth estimated using a linear poroelasticity model
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DOI：
10.1016/s0026-2862(03)00057-8
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发表时间：
2003-11-01
影响因子：
3.1
通讯作者：
Jain, RK
中科院分区：
文献类型：
--
作者：
Roose, T;Netti, PA;Jain, RK
实体瘤的不受控制的生长产生固体应力，导致周围组织变形。这种压力可能导致临床并发症，特别是在封闭的环境中，如大脑，也可能导致病理生理异常，如血管和淋巴管的塌陷。高应激水平也可能抑制肿瘤内的进一步细胞分裂。不幸的是，我们对肿瘤中压力积累的动力学及其对细胞生物学的影响知之甚少。我们提出了一个数学模型，肿瘤生长在一个有限的，弹性的环境，如活组织。该模型是根据热膨胀理论开发的，使用材料元件的当前配置，可以计算生长中的肿瘤和周围介质中的应力。实验观察到封闭环境限制肿瘤球体的生长小于营养扩散所施加的限制被纳入模型中，使用应力依赖的肿瘤生长速率。针对VII型琼脂糖凝胶中MU89肿瘤球状体生长的实验验证该模型。使用的数学模型和实验证据，我们表明，肿瘤细胞的大小减少了肿瘤球体内的固体应力。这导致了一种有趣的可能性，即细胞大小可能是临床环境中肿瘤内部固体应力水平的直接指标。(C)2003年爱思唯尔公司All rights reserved.
The unchecked growth of a solid tumor produces solid stress, causing deformation of the surrounding tissue. This stress can result in clinical complications, especially in confined environments such as the brain, and may also be responsible for pathophysiological anomalies such as the collapse of blood and lymphatic vessels. High stress levels may also inhibit further cell division within tumors. Unfortunately, little is known about the dynamics of stress accumulation in tumors or its effects on cell biology. We present a mathematical model for tumor growth in a confined, elastic environment such as living tissue. The model, developed from theories of thermal expansion using the current configuration of the material element, allows the stresses within the growing tumor and the surrounding medium to be calculated. The experimental observation that confining environments limit the growth of tumor spheroids to less than the limit imposed by nutrient diffusion is incorporated into the model using a stress dependent rate for tumor growth. The model is validated against experiments for MU89 tumor spheroid growth in Type VII agarose gel. Using the mathematical model and the experimental evidence we show that the tumor cell size is reduced by solid stress inside the tumor spheroid. This leads to the interesting possibility that cell size could be a direct indicator of solid stress level inside the tumors in clinical setting. (C) 2003 Elsevier Inc. All rights reserved.