Flow induces epithelial-mesenchymal transition, cellular heterogeneity and biomarker modulation in 3D ovarian cancer nodules

• DOI: 10.1073/pnas.1216989110
• Publication Date: 2013-05-04T04:28:49Z
• Authors: Imran Rizvi; Umut A. Gurkan; Savas Tasoglu; Nermina Alagic; Jonathan P. Celli; Lawrence B. Mensah; Zhiming Mai; Utkan Demirci; Tayyaba Hasan
• Keywords: Ovarian tumor; Slug

Seventy-five percent of patients with epithelial ovarian cancer present advanced-stage disease that is extensively disseminated intraperitoneally and prognosticates the poorest outcomes. Primarily metastatic within abdominal cavity, carcinomas initially spread to adjacent organs by direct extension then disseminate via transcoelomic route distant sites. Natural fluidic streams malignant ascites triggered physiological factors, including gravity negative subdiaphragmatic pressure, carry cells throughout peritoneum. We investigated role forces as modulators biology in a customizable microfluidic platform using 3D nodules. Changes morphological, genetic, protein profiles biomarkers associated aggressive were evaluated cultures grown under controlled continuous laminar flow. A modulation biomarker expression tumor morphology consistent increased epithelial–mesenchymal transition, critical step progression an indicator disease, observed because hydrodynamic forces. The increase transition driven part posttranslational up-regulation epidermal growth factor receptor (EGFR) activation, which worst prognosis cancer. flow-induced, transcriptionally regulated decrease E-cadherin simultaneous vimentin observed, indicating potential. These findings demonstrate induce motile phenotype. developed here potentially provides flow-informed framework complementary conventional mechanism-based therapeutic strategies, broad applicability other lethal malignancies.