The Mechanics of Single Cell and Collective Migration of Tumor Cells

Abstract

Metastasis is a dynamic process in which cancer cells navigate the tumor microenvironment, largely guided by external chemical and mechanical cues. Our current understanding of metastatic cell migration has relied primarily on studies of single cell migration, most of which have been performed using two-dimensional (2D) cell culture techniques and, more recently, using three-dimensional (3D) scaffolds. However, the current paradigm focused on single cell movements is shifting toward the idea that collective migration is likely one of the primary modes of migration during metastasis of many solid tumors. Not surprisingly, the mechanics of collective migration differ significantly from single cell movements. As such, techniques must be developed that enable in-depth analysis of collective migration, and those for examining single cell migration should be adopted and modified to study collective migration to allow for accurate comparison of the two. In this review, we will describe engineering approaches for studying metastatic migration, both single cell and collective, and how these approaches have yielded significant insight into the mechanics governing each process.

The motogenic effect of EGF and TGF-α on the migration of tumor cells from the oral region

“…The wound healing (or scratch) assay is a popular 2-D in vitro assay to visualize collective cell migration that allows polarization, force generation, and mechanism of cell-cell adhesion to be studied during the movement of confluent monolayers. [30][31][32] Normal keratinocytes (HaCaT) were stimulated to migrate upon addition of TGF-a in the wound healing assay, whereas EGF was not able to stimulate normal keratinocytes to migrate. In this assay, TGF-a-induced normal keratinocytes migrated as single cells, the opposite to collective migration.…”

Interactive dynamics of matrix adhesion and reaction-diffusion predict diverse multiscale strategies of cancer cell invasion

“…The migratory dynamics of cancer epithelia can also transition among the abovementioned types: mesenchymal, amoeboid, and collective; such plasticity may further drive phenotypic heterogeneity and symbiotic behavior in cancer invasion patterns (Hecht et al, 2015;Huang et al, 2015;Lintz et al, 2017). As cancer cells migrate to newer microenvironments, transitions from mesenchymal to epithelial morphologies could appropriately render invasive single cells more adhesive to each other (Krakhmal et al, 2015).…”

Biomechanics of Collective Cell Migration in Cancer Progression: Experimental and Computational Methods

“…Spheroids are constituted by cells, either primary or from cell lines, aggregated in a 3D scaffold, usually from ECM proteins (collagen, fibrin, Matrigel, etc.) 101 .…”