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乳腺癌细胞在矩阵刚度的动态调节后表现出介质上皮质可塑性
Chinmay S Sankhe1, Jessica L Sacco1, Jacob Lawton1
1Department of Chemical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA.
这项研究开发了一个新的体外平台来研究使用动态水凝的介质细胞-上皮细胞过渡 (MET). 研究结果显示,矩阵刚度调节MET,影响癌细胞行为,并建议新的治疗点.
科学领域:
- 生物材料科学 生物材料科学
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
背景情况:
- 介质细胞-上皮细胞过渡 (MET) 对于癌症的发展和转移至关重要.
- 目前的体外模型缺乏通过机械线索研究MET调节的能力.
- 了解MET的机械调节对于发育生物学和瘤学都至关重要.
研究的目的:
- 为了合成一种基于氨酸的新型水凝平台,具有可调节的刚性.
- 调查矩阵力学在乳腺上皮细胞和乳腺癌细胞中MET调节中的作用.
- 探索度介导的MET对癌细胞增殖,细胞亡和基因表达的影响.
主要方法:
- 基于氨酸的动态和可调节硬度水凝的合成,模仿乳腺组织.
- 在这些水凝上培养乳腺上皮细胞和乳腺癌细胞.
- 分析细胞增殖,细胞亡,形态学,细胞骨组织和基因表达,以应对刚性变化.
- 调查整合素结合激酶 (ILK) 在矩阵刚度介导的MET中的作用.
主要成果:
- 逐渐的水凝软化减少了乳腺癌细胞的增殖和增加了细胞亡.
- 乳腺癌细胞表现出介质细胞-上皮质可塑性,以应对矩阵刚度的下降.
- 降低矩阵刚度减弱了整合因相关激酶表达,影响细胞行为.
- 在矩阵刚度介导的MET期间识别了中间的上皮/介质细胞状态.
结论:
- 动态凝刚性是介质细胞-上皮细胞可塑性的关键调节器.
- 矩阵力学在控制MET方面发挥着重要作用,对癌症转移有影响.
- 整合素结合激酶是细胞在MET期间对矩阵刚性的反应的关键调解剂.
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