Cells making their own EGF (orange) migrate better than those supplied with exogenous EGF (green).

On page 1123, Maheshwari et al. show that the way a growth factor is delivered to a cell can profoundly affect the cell's response. The work supports a new model for mammary epithelial cell migration in response to EGF stimulation, and suggests that growth factor-based therapies may be destined to fail if they are not presented to cells correctly.

The authors previously developed an experimental system in which mammary epithelial cells expressing the EGF receptor (EGFR) can be stimulated by EGF through autocrine, paracrine, or intracrine mechanisms. In the new work, autocrine stimulation, in which EGF is secreted from the cells to bind its receptor on the cell surface, causes the cells to migrate rapidly with persistent direction. But adding EGF protein exogenously for paracrine stimulation, or expressing a processed form of the growth factor to bind to the EGFR pool inside the cell (intracrine stimulation) both cause a “scattering” response in which the cells lack directional persistence.The results suggest that autocrine stimulation provides directionality, possibly by localized formation of EGF–EGFR signaling complexes on the cell surface. It also seems that biotechnologists hoping to exploit growth factors for tasks ranging from tissue engineering to cancer therapy may need to work on their delivery. ▪