Tumor spheroid chemotaxis in epidermal growth factor gradients revealed by a 3D microfluidic platform*

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 embedded within a 3D collagen matrix displayed enhanced motility but no discernable chemotaxis in the presence of 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 ECM in the presence of EGF gradients. We found that EGF gradients promoted tumor cells to detach from the spheroid core, and the position of the tumor spheroid core showed a mild chemotactic response towards the EGF gradients. In addition, tumor cells detached from the spheroids showed significant chemokinesis but no discernable chemotactic response towards the EGF gradients. This work demonstrated that a cluster of tumor cells respond differently than single tumor cells towards EGF gradients and highlighted the importance of a tumor spheroid platform for chemotaxis studies.