Resistance to Fluid Shear Stress Is a Conserved Biophysical Property of Malignant Cells

Resistance to Fluid Shear Stress Is a Conserved Biophysical Property of Malignant Cells
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DOI:
10.1371/journal.pone.0050973
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发表时间:
2012-12-03
期刊:
影响因子:
3.7
通讯作者:
Henry, Michael D.
Henry, Michael D.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Barnes, J. Matthew;Nauseef, Jones T.;Henry, Michael D.

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在转移过程中,癌细胞进入循环以进入远端组织,但这种流体微环境如何影响癌细胞生物学尚不清楚。长期以来的观点是,来自实体组织的循环癌细胞可能容易受到血流动力学剪切力的损伤,从而导致转移效率低下。在这里,我们报告了与未转化的上皮细胞相比,转化细胞在微流控方案中对流体剪切应力(FSS)具有显著的抵抗力,当受到一系列高FSS的毫秒脉冲时,表现出活力的双相下降。我们发现FSS耐药性的大小受到几个癌基因的影响,是一种由质膜损伤触发的适应性和短暂反应,需要细胞外钙和肌动蛋白细胞骨架动力学。恶性癌细胞的这种新特性可能促进血液转移,并表明,与预期相反,癌细胞对血流动力学剪切力的破坏具有相当的抵抗力。引文:Barnes JM, Nauseef JT, Henry MD(2012)对流体剪切应力的抵抗是恶性细胞的一种保守的生物物理特性。科学通报,7(12):850973。doi: 10.1371 / journal.pone.0050973
During metastasis, cancer cells enter the circulation in order to gain access to distant tissues, but how this fluid microenvironment influences cancer cell biology is poorly understood. A longstanding view is that circulating cancer cells derived from solid tissues may be susceptible to damage from hemodynamic shear forces, contributing to metastatic inefficiency. Here we report that compared to non-transformed epithelial cells, transformed cells are remarkably resistant to fluid shear stress (FSS) in a microfluidic protocol, exhibiting a biphasic decrease in viability when subjected to a series of millisecond pulses of high FSS. We show that magnitude of FSS resistance is influenced by several oncogenes, is an adaptive and transient response triggered by plasma membrane damage and requires extracellular calcium and actin cytoskeletal dynamics. This novel property of malignant cancer cells may facilitate hematogenous metastasis and indicates, contrary to expectations, that cancer cells are quite resistant to destruction by hemodynamic shear forces. Citation: Barnes JM, Nauseef JT, Henry MD (2012) Resistance to Fluid Shear Stress Is a Conserved Biophysical Property of Malignant Cells. PLoS ONE 7(12): e50973. doi: 10.1371/journal.pone.0050973