Combining Top-Down and Bottom-Up: An Open Microfluidic Microtumor Model for Investigating Tumor Cell-ECM Interaction and Anti-Metastasis

Abstract

Using a combined top-down (i.e., operator-directed) and bottom-up (i.e., cell-directed) strategy, we present an Under-oil Open Microfluidic System (UOMS)-based microtumor model for investigating tumor cell migration and anti-metastasis drug test. Compared to the mainstream closed microfluidics-based microtumor models, the UOMS microtumor model features: i) micrometer-scale lateral resolution of surface patterning with open microfluidic design for flexible spatiotemporal sample manipulation (i.e., top-down); ii) self-organized extracellular matrix (ECM) structures and tumor cell-ECM spontaneous remodeling (i.e., bottom-up); and iii) free physical access to the samples on a device with minimized system disturbance. The UOMS microtumor model is used to test an anti-metastasis drug (incyclinide, aka CMT-3) with a triple negative breast cancer cell line (MDA-MB-231). Thein vitroresults show a suppression of tumor cell migration and ECM remodeling echoing with thein vivomice metastasis results.