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周期性拉伸诱导的 1 Hz 频率机械应力可改变 SAOS-2 骨肉瘤细胞的转移潜能特性。

Cyclic Stretch-Induced Mechanical Stress Applied at 1 Hz Frequency Can Alter the Metastatic Potential Properties of SAOS-2 Osteosarcoma Cells.

机构信息

Department of Clinical Sciences and Translational Medicine, University of Rome 'Tor Vergata', Via Montpellier 1, I-00133 Rome, Italy.

Institute of Structure Matter del Consiglio Nazionale delle Ricerche ISM-CNR, Via del Fosso del Cavaliere 100, I-00133 Rome, Italy.

出版信息

Int J Mol Sci. 2023 Apr 22;24(9):7686. doi: 10.3390/ijms24097686.

Abstract

Recently, there has been an increasing focus on cellular morphology and mechanical behavior in order to gain a better understanding of the modulation of cell malignancy. This study used uniaxial-stretching technology to select a mechanical regimen able to elevate SAOS-2 cell migration, which is crucial in osteosarcoma cell pathology. Using confocal and atomic force microscopy, we demonstrated that a 24 h 0.5% cyclic elongation applied at 1 Hz induces morphological changes in cells. Following mechanical stimulation, the cell area enlarged, developing a more elongated shape, which disrupted the initial nuclear-to-cytoplasm ratio. The peripheral cell surface also increased its roughness. Cell-based biochemical assays and real-time PCR quantification showed that these morphologically induced changes are unrelated to the osteoblastic differentiative grade. Interestingly, two essential cell-motility properties in the modulation of the metastatic process changed following the 24 h 1 Hz mechanical stimulation. These were cell adhesion and cell migration, which, in fact, were dampened and enhanced, respectively. Notably, our results showed that the stretch-induced up-regulation of cell motility occurs through a mechanism that does not depend on matrix metalloproteinase (MMP) activity, while the inhibition of ion-stretch channels could counteract it. Overall, our results suggest that further research on mechanobiology could represent an alternative approach for the identification of novel molecular targets of osteosarcoma cell malignancy.

摘要

最近,人们越来越关注细胞形态和机械行为,以更好地理解细胞恶性程度的调节。本研究采用单轴拉伸技术选择了一种能够提高 SAOS-2 细胞迁移的力学方案,这在骨肉瘤细胞病理学中至关重要。通过共聚焦和原子力显微镜,我们证明了施加 1 Hz 的 24 h 0.5%周期性伸长会引起细胞形态变化。在机械刺激后,细胞面积增大,形状变得更加细长,从而破坏了初始的核质比。外周细胞表面也增加了粗糙度。基于细胞的生化测定和实时 PCR 定量显示,这些形态诱导的变化与成骨细胞分化程度无关。有趣的是,在调节转移过程中,两种重要的细胞运动特性在 24 h 1 Hz 的机械刺激后发生了变化。这是细胞黏附和细胞迁移,实际上分别受到抑制和增强。值得注意的是,我们的结果表明,拉伸诱导的细胞运动上调是通过一种不依赖于基质金属蛋白酶(MMP)活性的机制发生的,而抑制离子拉伸通道可以抵消这种作用。总的来说,我们的研究结果表明,进一步研究机械生物学可能为骨肉瘤细胞恶性程度的新分子靶点的鉴定提供一种替代方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26a4/10178551/13c43ef0e382/ijms-24-07686-g001.jpg

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