Lymphoidal chemokine CCL19 promoted the heterogeneity of the breast tumor cell motility within a 3D microenvironment revealed by a Lévy distribution analysis

Abstract

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.