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, an Under-oil Open Microfluidic System (UOMS)-based microtumor model is presented 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 - allowing a controlled but also self-organized, cell-directed tumor-ECM microenvironment in an open microfluidic configuration - is used to test an anti-metastasis drug (incyclinide, aka CMT-3) with a triple-negative breast cancer cell line (MDA-MB-231). The in vitro results show a suppression of tumor cell migration and ECM remodeling echoing the in vivo mice metastasis results.

Keywords: ECM alignment&remodeling; anti‐metastasis; cell migration; open microfluidics; tumor microenvironment.