Cancer Cell Stiffness: Integrated Roles of Three-Dimensional Matrix Stiffness and Transforming Potential
Cancer Cell Stiffness: Integrated Roles of Three-Dimensional Matrix Stiffness and Transforming Potential
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DOI：
10.1016/j.bpj.2010.07.051
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发表时间：
2010-10-06
影响因子：
3.4
通讯作者：
Zaman, Muhammad H.
中科院分区：
文献类型：
--
作者：
Baker, Erin L.;Lu, Jing;Zaman, Muhammad H.
虽然在揭示影响乳腺癌进展的分子机制方面取得了重大进展，但对相关的细胞机械特性知之甚少。为此，我们使用粒子跟踪微流变学来研究乳腺上皮细胞（MEC）癌症进展系列中细胞内力学、三维基质刚度和转化潜力之间的相互作用。我们使用了一个充分表征的模型系统，其中人源MCF 10A MEC过表达ErbB 2、14-3-3 zeta或ErbB 2和14-3-3 zeta两者，空载体作为对照。我们的研究结果表明，具有ErbB 2转化潜力的MEC对基质硬度升高有反应，而未转化的MEC或仅过表达14-3-3 zeta的MEC没有表现出这种反应。我们进一步观察到ErbB 2单独过表达与细胞内对基质硬度的最高程度敏感性相关，并且转化电位对细胞内硬度的影响是基质硬度依赖性的。此外，我们的细胞内刚度测量平行的细胞迁移行为，已报告这些MEC亚系。鉴于目前的知识基础的乳腺癌机械生物学，这些研究结果表明，可能有一个积极的关系之间的细胞内刚度敏感性，细胞运动性和扰动mechanotransduction在乳腺癌。
While significant advances have been made toward revealing the molecular mechanisms that influence breast cancer progression, much less is known about the associated cellular mechanical properties. To this end, we use particle-tracking microrheology to investigate the interplay among intracellular mechanics, three-dimensional matrix stiffness, and transforming potential in a mammary epithelial cell (MEC) cancer progression series. We use a well-characterized model system where human-derived MCF10A MECs overexpress either ErbB2, 14-3-3 zeta, or both ErbB2 and 14-3-3 zeta, with empty vector as a control. Our results show that MECs possessing ErbB2 transforming potential stiffen in response to elevated matrix stiffness, whereas non-transformed MECs or those overexpressing only 14-3-3 zeta do no exhibit this response. We further observe that overexpression of ErbB2 alone is associated with the highest degree of intracellular sensitivity to matrix stiffness, and that the effect of transforming potential on intracellular stiffness is matrix-stiffness-dependent. Moreover, our intracellular stiffness measurements parallel cell migration behavior that has been previously reported for these MEC sublines. Given the current knowledge base of breast cancer mechanobiology, these findings suggest that there may be a positive relationship among intracellular stiffness sensitivity, cell motility, and perturbed mechanotransduction in breast cancer.