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流体切应力会影响卵巢癌细胞活力、亚细胞结构,并促进基因组不稳定性。

Fluid shear stress impacts ovarian cancer cell viability, subcellular organization, and promotes genomic instability.

机构信息

School of Biomedical Engineering and Sciences, Virginia Tech - Wake Forest University, Blacksburg, VA, United States of America.

Department of Human Nutrition, Foods and Exercise, Virginia Tech, Blacksburg, VA, United States of America.

出版信息

PLoS One. 2018 Mar 22;13(3):e0194170. doi: 10.1371/journal.pone.0194170. eCollection 2018.

Abstract

Ovarian cancer cells are exposed to physical stress in the peritoneal cavity during both tumor growth and dissemination. Ascites build-up in metastatic ovarian cancer further increases the exposure to fluid shear stress. Here, we used a murine, in vitro ovarian cancer progression model in parallel with immortalized human cells to investigate how ovarian cancer cells of increasing aggressiveness respond to [Formula: see text] of fluid-induced shear stress. This biophysical stimulus significantly reduced cell viability in all cells exposed, independent of disease stage. Fluid shear stress induced spheroid formation and altered cytoskeleton organization in more tumorigenic cell lines. While benign ovarian cells appeared to survive in higher numbers under the influence of fluid shear stress, they exhibited severe morphological changes and chromosomal instability. These results suggest that exposure of benign cells to low magnitude fluid shear stress can induce phenotypic changes that are associated with transformation and ovarian cancer progression. Moreover, exposure of tumorigenic cells to fluid shear stress enhanced anchorage-independent survival, suggesting a role in promoting invasion and metastasis.

摘要

在肿瘤生长和扩散过程中,卵巢癌细胞会在腹腔中受到物理压力。转移性卵巢癌腹水的积聚进一步增加了它们对流体切应力的暴露。在这里,我们使用了一种鼠的、体外卵巢癌进展模型,同时使用了永生化的人类细胞,以研究侵袭性不断增加的卵巢癌细胞如何对[公式:见正文]的流体诱导切应力做出反应。这种生物物理刺激显著降低了所有暴露细胞的活力,而与疾病阶段无关。流体切应力诱导了球形形成,并改变了更具肿瘤形成能力的细胞系中的细胞骨架组织。虽然良性卵巢细胞在流体切应力的影响下似乎以更高的数量存活,但它们表现出严重的形态变化和染色体不稳定性。这些结果表明,良性细胞暴露于低幅度的流体切应力会引起与转化和卵巢癌进展相关的表型变化。此外,肿瘤细胞暴露于流体切应力增强了非锚定依赖性存活,提示其在促进侵袭和转移中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2a9/5864000/95551388def2/pone.0194170.g001.jpg

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