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Solid tumors are poroelastic solids with a chemo–mechanical feedback on growth

机译:实体瘤是多孔的固体对生长具有化学机械反馈

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摘要

The experimental evidence that a feedback exists between growth and stress in tumors poses challenging questions. First, the rheological properties (the “constitutive equations”) of aggregates of malignant cells are still a matter of debate. Secondly, the feedback law (the “growth law”) that relates stress and mitotic-apoptotic rate is far to be identified. We address these questions on the basis of a theoretical analysis of in vitro and in vivo experiments that involve the growth of tumor spheroids. We show that solid tumors exhibit several mechanical features of a poroelastic material, where the cellular component behaves like an elastic solid. When the solid component of the spheroid is loaded at the boundary, the cellular aggregate grows up to an asymptotic volume that depends on the exerted compression. Residual stress shows up when solid tumors are radially cut, highlighting a peculiar tensional pattern. By a novel numerical approach we correlate the measured opening angle and the underlying residual stress in a sphere. The features of the mechanobiological system can be explained in terms of a feedback of mechanics on the cell proliferation rate as modulated by the availability of nutrient, that is radially damped by the balance between diffusion and consumption. The volumetric growth profiles and the pattern of residual stress can be theoretically reproduced assuming a dependence of the target stress on the concentration of nutrient which is specific of the malignant tissue.
机译:在肿瘤的生长与压力之间存在反馈的实验证据提出了具有挑战性的问题。首先,恶性细胞聚集体的流变特性(“本构方程”)仍是一个有争议的问题。其次,与压力和有丝分裂-细胞凋亡率相关的反馈定律(“生长定律”)尚待确定。我们在涉及肿瘤球体生长的体外和体内实验的理论分析的基础上解决这些问题。我们显示实体瘤表现出多孔弹性材料的几个机械特征,其中细胞成分的行为像弹性固体。当球体的固体成分加载到边界时,细胞聚集体长大到取决于施加的压缩的渐近体积。放射状切开实体瘤时会出现残余应力,突出了特殊的张力模式。通过一种新颖的数值方法,我们可以将测得的打开角度与球体中的潜在残余应力相关联。可以通过力学对细胞增殖速率的反馈来解释机械生物系统的特征,该反馈受营养物的可用性调节,其在径向上受到扩散和消耗之间的平衡的抑制。假设目标应力对恶性组织特有的营养物浓度具有依赖性,则理论上可以再现体积生长曲线和残余应力的模式。

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