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Lymphoidal chemokine CCL19 promoted the heterogeneity of the breast tumor cell motility within a 3D microenvironment revealed by a Lévy distribution analysis.
Integrative Biology ( IF 2.5 ) Pub Date : 2020-02-22 , DOI: 10.1093/intbio/zyaa001
Beum Jun Kim 1 , Pimkhuan Hannanta-Anan 1, 2 , Anders Ryd 3 , Melody A Swartz 4 , Mingming Wu 1
Affiliation  

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.

中文翻译:

Lévy 分布分析显示,淋巴趋化因子 CCL19 促进了 3D 微环境中乳腺肿瘤细胞运动的异质性。

肿瘤细胞异质性,无论是在基因型还是表型水平上,都是癌症的标志。即使在同一来源的细胞之间,肿瘤细胞也表现出很大的差异,包括细胞形态、速度和运动类型。然而,目前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(一种社会科学和物理科学中已知的用于量化罕见事件的方法)来表征肿瘤细胞运动的异质性。具体来说,我们研究了使用微流体平台对乳腺肿瘤细胞(MDA-MB-231 细胞系)进行明确的淋巴趋化因子 (CCL19) 梯度时的速度统计。实验结果表明,Lévy函数很好地描述了乳腺肿瘤细胞速度分布的尾部。测量的 Lévy 指数显示,当 CCL19 浓度接近与其相应受体 CCR7 的动态动力学结合常数时,细胞运动更加异质。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方面的重要性。
更新日期:2020-02-24
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