Modulation of the Invasive Phenotype of Engineered Breast Tumors by the Physical and Cellular Microenvironment

Abstract

Tumor development alters the normal cellular processes that maintain tissue integrity and homeostasis, and introduces changes to the tissue surrounding the tumor as well as the tumor cells themselves. Tumor development and invasion are regulated by the physical and chemical properties of the interstitial microenvironment. Here, we examined the effects of both interstitial fluid pressure and vascular endothelial cells on the invasive phenotype of engineered three-dimensional (3D) aggregates of MDA-MB-231 human breast cancer cells. The directionality of the interstitial pressure profile and the presence of endothelial cells altered the frequency at which cells invaded from the surface of the aggregate. Moreover, introducing pressure at one end of an aggregate suppressed invasion at the opposite end. We found previously that elevated interstitial pressure inhibits invasion by altering the chemical composition of the interstitial fluid near the surface of the aggregate. Our data reveal a link between hydrostatic pressure, the vascular endothelium, interstitial convection, and invasion.