Circulating prostate cancer cells have differential resistance to fluid shear stress-induced cell death.

Circulating prostate cancer cells have differential resistance to fluid shear stress-induced cell death.
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DOI:
10.1242/jcs.251470
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发表时间:
2021-02-22
影响因子:
4
通讯作者:
King MR
King MR
中科院分区:
生物学2区
文献类型:
--
作者:
Hope JM;Bersi MR;Dombroski JA;Clinch AB;Pereles RS;Merryman WD;King MR

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循环肿瘤细胞(CTCs)在循环中暴露于大于1000 dyn/cm2 (100 Pa)的流体剪切应力(FSS)。通常情况下,ctc暴露于这种程度的FSS会死亡。然而,一些ctc对这种FSS产生耐药性,使它们能够在远处的器官上定植。我们探讨了前列腺ctc如何在这种强度的力量下抵抗细胞死亡。DU145、PC3和LNCaP人类前列腺癌细胞系被用来代表不同转移来源的细胞。用30g针和注射泵短暂处理细胞系,平均FSS为3950 dyn/cm2 (395 Pa)。DU145细胞活力无变化,PC3细胞有一定程度的细胞死亡,LNCaP细胞有明显的细胞死亡。这些细胞死亡反应与细胞膜损伤增加、膜修复效率降低和僵硬增加有关。此外,FSS治疗可以阻止LNCaP FSS敏感细胞系在体内形成生长的肿瘤。这表明这些特性在FSS耐药性中起作用,并可能代表破坏血源性转移的潜在靶点。总结:前列腺癌细胞对流体力有不同的敏感性,这改变了它们对血流量水平流体剪切应力升高的抵抗力。
Circulating tumor cells (CTCs) are exposed to fluid shear stress (FSS) of greater than 1000 dyn/cm2 (100 Pa) in circulation. Normally, CTCs that are exposed to FSS of this magnitude die. However, some CTCs develop resistance to this FSS, allowing them to colonize distant organs. We explored how prostate CTCs can resist cell death in response to forces of this magnitude. The DU145, PC3 and LNCaP human prostate cancer cell lines were used to represent cells of different metastatic origins. The cell lines were briefly treated with an average FSS of 3950 dyn/cm2 (395 Pa) using a 30 G needle and a syringe pump. DU145 cells had no change in cell viability, PC3 cells had some cell death and LNCaP cells exhibited significant cell death. These cell death responses correlated with increased cell membrane damage, less efficient membrane repair and increased stiffness. Additionally, FSS treatment prevented the LNCaP FSS-sensitive cell line from forming a growing tumor in vivo. This suggests that these properties play a role in FSS resistance and could represent potential targets for disrupting blood-borne metastasis. Summary: Prostate cancer cells have different sensitivities to fluid forces that alter their resistance to elevated blood flow-level fluid shear stress.
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