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抗肿瘤药物对 ER 阳性 MCF-7 和 HER2 阳性 SKBR-3 乳腺癌细胞生物力学的影响。

The Impact of Anti-tumor Agents on ER-Positive MCF-7 and HER2-Positive SKBR-3 Breast Cancer Cells Biomechanics.

机构信息

Laboratory of Biomechanics and Biomedical Engineering, Department of Mechanical Engineering and Aeronautics, University of Patras, Rion, 26504, Patra, Greece.

Clinical Oncology Laboratory, Division of Oncology, Department of Medicine, University of Patras, Rion, 26504, Patra, Greece.

出版信息

Ann Biomed Eng. 2019 Aug;47(8):1711-1724. doi: 10.1007/s10439-019-02284-3. Epub 2019 May 16.

Abstract

Studying human cancer from a biomechanical perspective may contribute to pathogenesis understanding which leads to the malignancy. In this study, biomechanics of suspended and adhered breast cancer cells were investigated via the micropipette aspiration method with special emphasis on comparing the cell stiffness and viscoelastic parameters of estrogen receptor positive, ER+, MCF-7 and human epidermal growth factor receptor 2 positive, HER2 +, SKBR-3 cancer cell lines prior to and post treatment with tamoxifen and trastuzumab, respectively. Alterations of mechanical parameters included significant increase in cell stiffness, especially after treatment with trastuzumab and changes in viscoelastic parameters, in both cancer cell lines post treatment. According to immunofluorescence analysis, the raised cell stiffness was corresponded to remodeling of F-actin, which peripherally located in tamoxifen treated and perinuclear accumulated in trastuzumab treated cancer cell cytoskeleton, implying a reduced potential for cell deformation and motility. Additionally, these results were in line with the study of single and collective cell migration through Boyden chamber and wound healing assays respectively, where the potential for migration was significantly decreased after treatment. Consequently, these findings lead to an increased interest in biomechanics of cancer progression after treatment with anti-tumor agents, importantly in understanding the effect of the alterations of mechanical properties upon the possibility for change in metastatic potential.

摘要

从生物力学角度研究人类癌症可能有助于理解导致恶性肿瘤的发病机制。在这项研究中,我们通过微管吸吮法研究了悬浮和黏附乳腺癌细胞的生物力学特性,特别强调了比较雌激素受体阳性(ER+)的 MCF-7 和人表皮生长因子受体 2 阳性(HER2+)的 SKBR-3 癌细胞系在分别用他莫昔芬和曲妥珠单抗治疗前后的细胞硬度和粘弹性参数。力学参数的变化包括细胞硬度的显著增加,尤其是在用曲妥珠单抗治疗后,以及两种癌细胞系的粘弹性参数的变化。根据免疫荧光分析,细胞硬度的升高与 F-肌动蛋白的重塑相对应,在他莫昔芬处理的细胞中 F-肌动蛋白位于细胞外周,在曲妥珠单抗处理的细胞中 F-肌动蛋白在核周积累,这表明细胞变形和迁移的潜力降低。此外,这些结果与通过 Boyden 室和划痕愈合测定法研究单细胞和细胞群迁移的研究结果一致,其中在治疗后迁移的潜力显著降低。因此,这些发现导致人们对肿瘤治疗后癌症进展的生物力学产生了更大的兴趣,重要的是,这些发现有助于理解力学特性的变化对转移潜力变化的可能性的影响。

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