  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.
