Tumor spheroid invasion in epidermal growth factor gradients revealed by a 3D microfluidic device

Young Joon Suh, Mrinal Pandey, Jeffrey E. Segall, Mingming Wu

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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 motility 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 tumor invasion studies.

Original languageEnglish (US)
Article number036002
JournalPhysical Biology
Volume19
Issue number3
DOIs
StatePublished - May 1 2022

Keywords

  • 3D ECM
  • EGF
  • chemotaxis
  • invasion
  • microfluidics
  • tumor microenvironment
  • tumor spheroid

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Molecular Biology
  • Cell Biology

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