Nanotopography as Artificial Microenvironment for Accurate Visualization of Metastasis Development via Simulation of ECM Dynamics.

ABSTRACT

Metastatic progression is mediated by complex interactions between deregulated extracellular matrix (ECM) and cancer cells and remains a major challenge in cancer management. To investigate the role of ECM dynamics in promoting metastasis development, we developed an artificial microenvironment (AME) platform comprised of nanodot arrays of increasing diameter. Cells cultured on the platform showed increasing signs of mesenchymal-like cell transition as AME diameter increased, suggesting accurate simulation of ECM-mediated gene regulation. Gene expression was analyzed to determine genes significant to transition, which were then used to select appropriate small molecule drugs for time course treatments. Our results suggest that the platform can identify critical target genes as well as possible drug candidates. Overall, the AME platform allows for the study of intricate ECM-induced gene expression trends across metastasis development that would otherwise be difficult to visualize in vivo and may open new avenues toward successful personalized cancer management.