(509a) Interstitial Fluid Pressure Modulates Gene Expression in Engineered Models of Breast Tumors

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. Moreover, tumorigenesis and invasion are regulated by both the physical and chemical properties of the interstitial microenvironment. Here, we examined the effects of interstitial fluid pressure (IFP) on the expression of both epithelial and mesenchymal genes in engineered three-dimensional (3D) aggregates of MDA-MB-231 human breast cancer cells. We found using experimental analysis and finite element computational models that the pressure-induced convection of tumor-conditioned media from the base to the tip of the cell aggregate controlled the invasive phenotype at the tip. This suggests that IFP affects the migratory and invasive phenotype of cancer cells. It is therefore likely that IFP affects the expression of genes related to the invasive phenotype. Mesenchymal gene expression in particular is expected to be altered by IFP.