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Alterations in cancer cell mechanical properties after fluid shear stress exposure: a micropipette aspiration study

机译:流体剪切应力暴露后癌细胞力学性能的变化:微量移液器吸取研究

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Abstract: Over 90% of cancer deaths result not from primary tumor development, but from metastatic tumors that arise after cancer cells circulate to distal sites via the circulatory system. While it is known that metastasis is an inefficient process, the effect of hemodynamic parameters such as fluid shear stress (FSS) on the viability and efficacy of metastasis is not well understood. Recent work has shown that select cancer cells may be able to survive and possibly even adapt to FSS in vitro. The current research seeks to characterize the effect of FSS on the mechanical properties of suspended cancer cells in vitro. Nontransformed prostate epithelial cells (PrEC LH) and transformed prostate cancer cells (PC-3) were used in this study. The Young's modulus was determined using micropipette aspiration. We examined cells in suspension but not exposed to FSS (unsheared) and immediately after exposure to high (6,400 dyn/cm2) and low (510 dyn/cm2) FSS. The PrEC LH cells were ~140% stiffer than the PC-3 cells not exposed to FSS. Post-FSS exposure, there was an increase of ~77% in Young's modulus after exposure to high FSS and a ~47% increase in Young's modulus after exposure to low FSS for the PC-3 cells. There was no significant change in the Young's modulus of PrEC LH cells post-FSS exposure. Our findings indicate that cancer cells adapt to FSS, with an increased Young's modulus being one of the adaptive responses, and that this adaptation is specific only to PC-3 cells and is not seen in PrEC LH cells. Moreover, this adaptation appears to be graded in response to the magnitude of FSS experienced by the cancer cells. This is the first study investigating the effect of FSS on the mechanical properties of cancer cells in suspension, and may provide significant insights into the mechanism by which some select cancer cells may survive in the circulation, ultimately leading to metastasis at distal sites. Our findings suggest that biomechanical analysis of cancer cells could aid in identifying and diagnosing cancer in the future.
机译:摘要:超过90%的癌症死亡不是由原发性肿瘤发展引起的,而是由癌细胞通过循环系统循环到远端部位而引起的转移性肿瘤引起的。尽管已知转移是一个低效的过程,但对血流动力学参数(例如流体剪切应力(FSS))对转移的生存力和功效的影响尚不十分清楚。最近的工作表明,某些癌细胞可能能够存活,甚至可能在体外适应FSS。当前的研究试图表征FSS对体外悬浮癌细胞力学性能的影响。在这项研究中使用了未转化的前列腺上皮细胞(PrEC LH)和转化的前列腺癌细胞(PC-3)。杨氏模量使用微量移液器吸取来确定。我们检查了悬浮液中但未暴露于FSS(未剪切)的细胞以及暴露于高(6,400 dyn / cm2)和低(510 dyn / cm2)FSS后的细胞。 PrEC LH细胞比未暴露于FSS的PC-3细胞坚硬约140%。 FSS暴露后,PC-3细胞暴露于高FSS后杨氏模量增加了约77%,暴露于低FSS后杨氏模量增加了约47%。在FSS暴露后,PrEC LH细胞的杨氏模量没有显着变化。我们的发现表明癌细胞适应FSS,其中杨氏模量增加是适应性反应之一,并且这种适应性仅对PC-3细胞具有特异性,而在PrEC LH细胞中则未见。而且,这种适应性似乎是响应于癌细胞所经历的FSS的大小而分级的。这是第一项研究FSS对悬浮细胞癌细胞力学性能影响的研究,并且可能为某些癌细胞在循环中存活并最终导致远端部位转移的机制提供重要见解。我们的发现表明,对癌细胞的生物力学分析可能有助于将来识别和诊断癌症。

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