(175ab) Assessing Plasticity in Prostate Cancer Using Electrokinetic Techniques

Prostate cancer ranks as the second leading cause of mortality in men, with treatment challenges stemming from cellular plasticity, which intricately ties phenotypic shifts to chemoresistance. In this study, we employed a microfluidic device coupled with electrical impedance spectroscopy (EIS), an electrode-based cell characterization method, to investigate the electrical signatures of phenotype changes across various scenarios: (1) prostate cancer cell lines with different metastatic potentials (DU145, LNCaP, and PC3), (2) cells cultured in 2D monolayer versus 3D suspension, and (3) cells subjected to the anti-cancer drug nigericin. To corroborate observed phenotypic changes, we assessed the gene expression of epithelial markers E-cadherin (CDH1) and Zona Occuldens-1 (ZO-1). Our findings revealed distinct EIS profiles for each cell type and discernible differences between 2D and 3D cultures, indicating that electrical characteristics reflect in vitro cellular architecture. Moreover, EIS demonstrated its potential in identifying chemoresistant cells post-drug treatment. Furthermore, to capture true phenotype alterations, we induced the epithelial-to-mesenchymal transition (EMT), a known contributor to chemoresistance, and evaluated corresponding changes in electrical impedance. The results from this showed that EIS can distinguish between the DU145 EMT- and DU145 EMT+ cells and confirmed through immunofluorescence imaging. The PC3 EMT- and EMT+ cells did not show a distinct difference in EIS, based on the hypothesis that these cells mimic a mesenchymal phenotype. These results validate that EIS is a label-free, versatile tool that can be used to monitor phenotype changes in prostate cancer.