Alterations in cancer cell mechanical properties after fluid shear stress exposure: a micropipette aspiration study.
Alterations in cancer cell mechanical properties after fluid shear stress exposure: a micropipette aspiration study.
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流体剪切应力暴露后癌细胞机械特性的变化：微量移液器抽吸研究。
DOI：
10.2147/chc.s71852
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发表时间：
2015-01-09
期刊：
影响因子：
--
通讯作者：
Vigmostad SC
中科院分区：
文献类型：
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作者：
Chivukula VK;Krog BL;Nauseef JT;Henry MD;Vigmostad SC
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后出现的转移性肿瘤引起的。虽然已知转移是一个低效的过程，但血流动力学参数如流体剪切应力（FSS）对转移的存活力和功效的影响还没有很好地理解。最近的研究表明，选择的癌细胞可能能够在体外存活，甚至可能适应FSS。目前的研究旨在表征FSS对体外悬浮癌细胞力学性能的影响。本研究使用非转化前列腺上皮细胞（PrEC LH）和转化前列腺癌细胞（PC-3）。使用微量吸液管抽吸测定杨氏模量。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/cm 2）和低（510 dyn/cm 2）FSS后立即检查的细胞。PrEC LH细胞比未暴露于FSS的PC-3细胞硬约140%。暴露于FSS后，PC-3细胞暴露于高FSS后杨氏模量增加约77%，暴露于低FSS后杨氏模量增加约47%。FSS暴露后PrEC LH细胞的杨氏模量无显著变化。我们的研究结果表明，癌细胞适应FSS，增加杨氏模量的适应性反应之一，这种适应是特定的PC-3细胞，并没有看到在PrEC LH细胞。此外，这种适应似乎是根据癌细胞所经历的FSS的大小而分级的。这是第一项研究FSS对悬浮液中癌细胞机械特性的影响的研究，并可能对某些选定的癌细胞可能在循环中存活，最终导致远端部位转移的机制提供重要见解。我们的研究结果表明，癌细胞的生物力学分析可以帮助未来识别和诊断癌症。
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.