Tumor Spheroid Chemotaxis in Epidermal Growth Factor Gradients Revealed by a 3D Microfluidic Device

TL;DR

This study reveals that tumor spheroids exhibit a mild chemotactic response to EGF gradients and that cell detachment enhances chemokinesis, highlighting the importance of 3D spheroid models in chemotaxis research.

Contribution

It demonstrates that tumor cell clusters respond differently to EGF gradients than single cells, emphasizing the significance of spheroid models for studying tumor chemotaxis.

Findings

Tumor spheroids show a mild chemotactic response to EGF gradients.

Detached tumor cells exhibit enhanced chemokinesis.

Single cells within ECM do not show significant chemotaxis.

Abstract

Epidermal growth factor (EGF), a potent cytokine, is known to promote tumor invasion both in vivo and in vitro. Previously, we observed that single breast tumor cells (MDA-MB-231 cell line) embedded within a 3D collagen matrix displayed enhanced motility but no discernible chemotaxis in the presence of linear EGF gradients using a microfluidic platform. Inspired by a recent theoretical development that clustered mammalian cells respond differently to chemical gradients than single cells, we studied tumor spheroid invasion within a 3D extracellular matrix (ECM) in the presence of EGF gradients. We found that EGF gradients promoted tumor cell detachment from the spheroid core, and the position of the tumor spheroid core showed a mild chemotactic response towards the EGF gradients. For those tumor cells detached from the spheroids, they showed an enhanced chemokinesis response in contrast to previous experimental results using single cells embedded within an ECM. No discernible chemotactic response towards the EGF gradients was found for the cells outside the spheroid core. This work demonstrates that a cluster of tumor cells responds differently than single tumor cells towards EGF gradients and highlights the importance of a tumor spheroid platform for chemotaxis studies.