Metastatic cancer cells tenaciously indent impenetrable, soft substrates
Metastatic cancer cells tenaciously indent impenetrable, soft substrates
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DOI：
10.1088/1367-2630/15/3/035022
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发表时间：
2013-03-21
影响因子：
3.3
通讯作者：
Weihs, D.
中科院分区：
文献类型：
--
作者：
Kristal-Muscal, R.;Dvir, L.;Weihs, D.
我们在这里提出了转移性癌细胞机械渗透的第一个证据。在转移过程中，侵袭性癌细胞穿透组织和细胞外基质，改变形状并施加力。这些施加的力又取决于基材的硬度和降解性。转移性渗透的初始阶段包括基底压痕，然而，尚未对其进行研究。因此，我们评估了压痕的演变，重点关注与细胞转移潜力（MP）和基底硬度相关的差异。我们发现，转移细胞获得蘑菇样的形态，然后，在几个小时内，反复地以一种暗示细胞核的特殊作用的方式覆盖基质。具有较高MP的细胞先前已被证明比具有较低MP的细胞内部和外部更柔软，但矛盾的是，施加更强的力。较高MP的细胞在凝胶上产生更强的力，凝胶足够硬以提供抓握手柄，但足够软以粘附，而良性细胞根本不粘附底物。这些发现提供了对物理力在转移渗透的初始阶段的核心作用的深入了解，并揭示了新的治疗靶点。
We present here the first evidence of mechanical penetration by a metastatic cancer cell. During metastasis, the invasive cancer-cell penetrates tissue and extracellular matrix, changes shape and applies force. These applied forces, in turn, depend on substrate stiffness and degradability. The initial stage of metastatic penetration comprises substrate indentation, which, however, has not yet been studied. Hence, we evaluate the evolution of indentation, focusing on differences relating to the metastatic potential (MP) of the cells and substrate stiffness. We found that metastatic cells attain a mushroom-like morphology and then, over several hours, repeatedly indent the substrate in a manner suggestive of a special role for the nucleus. Cells with higher MP have previously been shown to be softer internally and externally than those with lower MP yet, paradoxically, applied stronger forces. Cells of higher MP develop stronger forces on gels stiff enough to provide grip handles yet soft enough to indent, whereas benign cells did not indent substrates at all. These findings provide insight into the central role of physical forces in the initial stages of metastatic penetration and reveal new targets for treatment.