The size-speed-force relationship governs migratory cell response to tumorigenic factors
The size-speed-force relationship governs migratory cell response to tumorigenic factors
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DOI：
10.1091/mbc.e16-10-0694
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发表时间：
2017-06-15
影响因子：
3.3
通讯作者：
Thery, Manuel
中科院分区：
文献类型：
--
作者：
Leal-Egana, Aldo;Letort, Gaelle;Thery, Manuel
肿瘤的发展是通过复杂的生物力学变化途径进行的，首先导致细胞生长和收缩，然后是细胞脱粘、分散和侵袭。致瘤因素可能对这些步骤之一起特异性作用，或者具有更广泛的作用谱，导致各种影响，因此有时会出现明显的矛盾结果。在这里，我们使用可变形表面上的I型胶原蛋白/纤连蛋白的微图案线来标准化细胞行为，并同时测量细胞大小、运动速度和单个细胞水平上的相关牵引力的大小。我们分析和比较了正常人乳腺细胞系MCF 10A在控制条件下，并在各种致瘤因素。在所有条件下，广泛的生物力学性能进行了鉴定。尽管存在这种异质性，正常和转化的运动细胞遵循一个共同的趋势，即大小和收缩力与细胞速度呈负相关。一些致瘤因素，如ErbB 2的激活或酪蛋白激酶2 β亚基的丢失，使整个群体转向更快的速度和更低的收缩状态。用转化生长因子β处理诱导一些细胞采取相反的行为，例如极高与极低的收缩性。因此，肿瘤转化放大了预先存在的群体异质性，并导致一些细胞表现出比正常细胞更极端的生物力学特性。
Tumor development progresses through a complex path of biomechanical changes leading first to cell growth and contraction and then cell deadhesion, scattering, and invasion. Tumorigenic factors may act specifically on one of these steps or have a wider spectrum of actions, leading to a variety of effects and thus sometimes to apparent contradictory outcomes. Here we used micropatterned lines of collagen type I/fibronectin on deformable surfaces to standardize cell behavior and measure simultaneously cell size, speed of motion and magnitude of the associated traction forces at the level of a single cell. We analyzed and compared the normal human breast cell line MCF10A in control conditions and in response to various tumorigenic factors. In all conditions, a wide range of biomechanical properties was identified. Despite this heterogeneity, normal and transformed motile cells followed a common trend whereby size and contractile forces were negatively correlated with cell speed. Some tumorigenic factors, such as activation of ErbB2 or loss of the beta subunit of casein kinase 2, shifted the whole population toward a faster speed and lower contractility state. Treatment with transforming growth factor beta induced some cells to adopt opposing behaviors such as extremely high versus extremely low contractility. Thus tumor transformation amplified preexisting population heterogeneity and led some cells to exhibit biomechanical properties that were more extreme than those observed with normal cells.