Living in shear: platelets protect cancer cells from shear induced damage
Living in shear: platelets protect cancer cells from shear induced damage
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DOI：
10.1007/s10585-014-9660-7
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发表时间：
2014-08-01
影响因子：
4
通讯作者：
Kenny, Dermot
中科院分区：
文献类型：
--
作者：
Egan, Karl;Cooke, Niamh;Kenny, Dermot
药物和基因导致的血小板减少与转移减少有关，突出了血小板在癌细胞血液传播中的重要性。人们经常认为，血小板支持转移，部分是通过保护癌细胞免受剪切力的影响，剪切力是一种由血液流动产生的生物力学力量。然而，目前还没有证据支持这一假设。为了解决这个问题，我们研究了在存在和不存在血小板的情况下切应力对A2780卵巢癌细胞的影响。使用锥板式粘度计，将含有和不含血小板的A2780细胞悬液分别置于代表静脉(200 S(-1))和动脉(1,500 S(-1))血流的切变率下。乳酸脱氢酶(LDH)释放量用于量化剪切性膜损伤。静脉和动脉切变率均可诱导A2780细胞释放乳酸脱氢酶，显示其对剪切力的敏感性。相比之下，血小板对类似情况的反应是释放最低水平的乳酸脱氢酶。在有血小板存在的情况下，A2780细胞在剪切条件下LDH的释放显著减少，这表明血小板对剪切损伤具有保护作用。在体内，血小板与癌细胞相互作用的中断会增加剪应力对癌细胞的破坏。
Pharmacologically and genetically induced thrombocytopenia is associated with decreased metastasis, highlighting the importance of platelets in the bloodborne dissemination of cancer cells. It is frequently suggested that platelets support metastasis, in part, by protecting cancer cells from shear stress, a biomechanical force generated by blood flow. However, there is currently no evidence to support this hypothesis. To address this, we investigated the effect of shear stress on A2780 ovarian cancer cells in the presence and absence of platelets. Using a cone and plate viscometer, suspensions of A2780 cells with and without platelets were exposed to shear rates representing venous (200 s(-1)) and arterial (1,500 s(-1)) blood flow. Lactate dehydrogenase (LDH) release was used to quantify shear induced membrane damage. Both venous and arterial shear rates induced the release of LDH from A2780 cells, demonstrating their susceptibility to shear forces. In contrast, platelets released minimal levels of LDH in response to similar conditions. In the presence of platelets, there was a significant decrease in LDH release by A2780 cells under shear conditions, suggesting that platelets can confer protection against shear induced damage. The disruption of platelet-cancer cell interactions could increase the shear stress induced destruction of cancer cells in vivo.