Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY, USA.
Department of Food Engineering, King Mongkut's Institute of Technology, Bangkok, Thailand.
Integr Biol (Camb). 2020 Feb 22;12(1):12-20. doi: 10.1093/intbio/zyaa001.
Tumor cell heterogeneity, either at the genotypic or the phenotypic level, is a hallmark of cancer. Tumor cells exhibit large variations, even among cells derived from the same origin, including cell morphology, speed and motility type. However, current work for quantifying tumor cell behavior is largely population based and does not address the question of cell heterogeneity. In this article, we utilize Lévy distribution analysis, a method known in both social and physical sciences for quantifying rare events, to characterize the heterogeneity of tumor cell motility. Specifically, we studied the breast tumor cell (MDA-MB-231 cell line) velocity statistics when the cells were subject to well-defined lymphoid chemokine (CCL19) gradients using a microfluidic platform. Experimental results showed that the tail end of the velocity distribution of breast tumor cell was well described by a Lévy function. The measured Lévy exponent revealed that cell motility was more heterogeneous when CCL19 concentration was near the dynamic kinetic binding constant to its corresponding receptor CCR7. This work highlighted the importance of tumor microenvironment in modulating tumor cell heterogeneity and invasion.
肿瘤细胞异质性，无论是在基因型还是表型水平上，都是癌症的一个标志。肿瘤细胞表现出很大的变化，即使是来自同一来源的细胞之间，也包括细胞形态、速度和运动类型。然而，目前用于量化肿瘤细胞行为的工作主要是基于群体的，并没有解决细胞异质性的问题。在本文中，我们利用 Lévy 分布分析，这是一种在社会和物理科学中都用于量化稀有事件的方法，来描述肿瘤细胞运动的异质性。具体来说，我们使用微流控平台研究了在淋巴趋化因子（CCL19）梯度作用下，乳腺肿瘤细胞（MDA-MB-231 细胞系）速度统计的 Lévy 分布。实验结果表明，乳腺肿瘤细胞速度分布的尾部可以很好地用 Lévy 函数来描述。测量得到的 Lévy 指数表明，当 CCL19 浓度接近其对应受体 CCR7 的动态动力学结合常数时，细胞的运动异质性更大。这项工作强调了肿瘤微环境在调节肿瘤细胞异质性和侵袭性方面的重要性。
