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首页> 外文期刊>American Journal of Physiology >Lamin A/C deficiency reduces circulating tumor cell resistance to fluid shear stress
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Lamin A/C deficiency reduces circulating tumor cell resistance to fluid shear stress

机译：Lamin A / C缺乏减少了流体剪切应力的循环肿瘤细胞抗性

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摘要

Metastasis contributes to over 90% of cancer-related deaths and is initiated when cancer cells detach from the primary tumor, invade the basement membrane, and enter the circulation as circulating tumor cells (CTCs). While metastasis is viewed as an inefficient process with most CTCs dying within the bloodstream, it is evident that some CTCs are capable of resisting hemodynamic shear forces to form secondary tumors in distant tissues. We hypothesized that nuclear lamins A and C (А/C) act as key structural components within CTCs necessary to resist destruction from elevated shear forces of the bloodstream. Herein, we show that, compared with nonmalignant epithelial cells, tumor cells are resistant to elevated fluid shear forces in vitro that mimic those within the bloodstream, as evidenced by significant decreases in cellular apoptosis and necrosis. Knockdown of lamin A/C significantly reduced tumor cell resistance to fluid shear stress, with significantly increased cell death compared with parental tumor cell and nontargeting controls. Interestingly, lamin A/C knockdown increased shear stress-induced tumor cell apoptosis, but did not significantly affect cellular necrosis. These data demonstrate that lamin A/C is an important structural component that enables tumor cell resistance to fluid shear stress-mediated death in the bloodstream, and may thus facilitate survival and hematogenous metastasis of CTCs.
机译：转移有助于超过90％的癌症相关死亡，并且当癌细胞从原发性肿瘤中脱节时，侵入地下室膜，并进入循环肿瘤细胞（CTC）的循环。虽然转移被视为具有血液内的大多数CTC的效率低下的过程，但很明显，一些CTC能够抵抗血液动力学剪切力以在远处组织中形成次级肿瘤。我们假设核叠层A和C（А/ C）作为抵抗血液升高的剪切力的破坏所必需的CTC中的关键结构组分。在此，我们表明，与非开始上皮细胞相比，肿瘤细胞对血液内血液中的体外升高的液体剪切力有抗性，如细胞凋亡和坏死的显着降低所证明。 Lamin A / C的敲低显着降低了肿瘤细胞对流体剪切应力的抗性，与家长肿瘤细胞和非靶向对照相比，细胞死亡显着增加。有趣的是，Lamin A / C敲低增加剪切应激诱导的肿瘤细胞凋亡，但没有显着影响细胞坏死。这些数据表明，Lamin A / C是一种重要的结构组分，使得能够在血液中能够对流体剪切应力介导的死亡进行肿瘤细胞抗性，因此可以促进CTC的存活和血液转移。

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