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The underlying difference of metastatic and non-metastatic breast cancer cells in configuring type I collagen fibres to promote migration by cell mechanics 转移性和非转移性乳腺癌细胞在配置I型胶原纤维通过细胞力学促进迁移方面的潜在差异
Pub Date : 2025-01-31 DOI: 10.1016/j.mbm.2025.100113
Mingxing Ouyang , Weihui Chen , Ting Zhou , Hongjie Liu , Lei Liu , Bing Bu , Linhong Deng
The progression of tumors is heavily influenced by mechanical properties of their microenvironment. In this work, we applied micropatterned models with varying distances and shapes to investigate the differences between metastatic MDA-MB-231 and non-metastatic MCF-7 breast cancer cells in reconfiguring extracellular matrix to promote cell migration induced by cell mechanics. Both cancer cells were able to rearrange type I collagen (COL) to form fibre threads, in which MDA-MB-231 consistently migrated more rapidly than MCF-7, ranging from geometrical square arrays with different spacings to complex polygonal models. MDA-MB-231 displayed higher capability of reorganizing fibre bundles at longer distance (800 ​μm). Further looking for differences in cell molecular mechanisms, siRNA knockdown inhibiting either integrin β1 or Piezo1 decreased fibre assembly and reduced the difference in COL remodeling and migration between two cancer cells. MDA-MB-231 showed inhibited migration with integrin knockdown, whereas scattering migration with Piezo1 knockdown, indicating cells losing directional mechanosensation. After inhibiting junctional E-cadherin with siRNA, MCF-7 cells migrated faster, resulting in reduced difference in comparison to MDA-MB-231 that didn't express E-cadherin. In summary, this work has explored the biomechanical differences between metastatic and non-metastatic breast cancer cells regarding COL fibre matrix remodeling and cell movements. The significant differences in E-cadherin expression in the two breast cancer cells had an effect on cell migrations. The results of this study provide research approaches for evaluating therapeutic effort on breast cancer.
肿瘤的发展在很大程度上受其微环境的力学特性的影响。在这项工作中,我们应用不同距离和形状的微图案模型来研究转移性MDA-MB-231和非转移性MCF-7乳腺癌细胞在细胞力学诱导的细胞外基质重新配置促进细胞迁移方面的差异。两种癌细胞都能够重新排列I型胶原蛋白(COL),形成纤维线,其中MDA-MB-231始终比MCF-7更快地迁移,范围从具有不同间距的几何方形阵列到复杂的多边形模型。MDA-MB-231在较远距离(800 μm)表现出较高的纤维束重组能力。进一步寻找细胞分子机制的差异,siRNA敲低抑制整合素β1或Piezo1减少了纤维组装,减少了两个癌细胞之间COL重塑和迁移的差异。MDA-MB-231在整合素敲低的情况下表现出被抑制的迁移,而在Piezo1敲低的情况下表现出散射迁移,表明细胞失去了定向机械感觉。用siRNA抑制连接E-cadherin后,MCF-7细胞迁移速度加快,与不表达E-cadherin的MDA-MB-231相比差异减小。总之,这项工作探讨了转移性和非转移性乳腺癌细胞在冷纤维基质重塑和细胞运动方面的生物力学差异。两种乳腺癌细胞中E-cadherin表达的显著差异对细胞迁移有影响。本研究结果为评价乳腺癌治疗效果提供了研究途径。
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引用次数: 0
Pub Date : 2025-01-01
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引用次数: 0
Pub Date : 2025-01-01
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Pub Date : 2025-01-01
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引用次数: 0
Pub Date : 2025-01-01
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引用次数: 0
Pub Date : 2025-01-01
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Pub Date : 2025-01-01
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Pub Date : 2025-01-01
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引用次数: 0
Pub Date : 2025-01-01
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引用次数: 0
Pub Date : 2025-01-01
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引用次数: 0
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Mechanobiology in Medicine
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