Fig. P1.

(A) This study was motivated by the need to identify the physical and biological factors that influence tumor heterogeneity within the context of ovarian cancer, an example of a lethal malignancy that disseminates and grows on stromal beds under the influence of preferential pathways of ascitic flow (blue arrows). (B) Ovarian cancer cells were cultured successfully under continuous flow for 7 d and formed viable micronodules in a custom bioengineered platform that integrates microfluidics and 3D tumor growth. (C) Flow-induced stress caused a posttranslational up-regulation of EGFR expression and activation, which may have resulted from decreased EGFR degradation and increased receptor recycling. The resulting increase in EGFR signaling led to a transcriptionally regulated decrease in E-cadherin protein expression. A concomitant significant decrease in β-catenin protein expression and increase in vimentin protein expression was observed.