Figure 2. Microenvironmental heterogeneity.
In normal tissues (such as normal breast) most epithelial cells experience similar concentrations of nutrients, oxygen, and growth factors. However, structural disorganization of epithelia, stroma, and vasculature leads to significant inequality in concentrations of these factors (one factor is illustrated). Further, differences in diffusion and consumption rates of different factors combinatorialy increase variability in microenvironmental cues directly influencing phenotypic heterogeneity and creating distinct selection forces.