Biomimetic Model of Tumor Microenvironment on Microfluidic Platform

The "Tumor microenvironment" (TME) is a complex, interacting system of the tumor and its surrounding environment. The TME has drawn more attention recently in attempts to overcome current drug resistance and the recurrence of cancer by understanding the cancer and its microenvironment systematically, beyond past reductionist approaches. However, a lack of experimental tools to dissect the intricate interactions has hampered in-depth research into the TME. Here, a biomimetic TME model using a microfluidic platform is presented, which enables the interaction between TME constituents to be studied in a comprehensive manner. Paracrine interactions of cocultured tumor cell lines (SK-OV-3, MKN-74, and SW620) with primary fibroblasts show marked morphological changes in the tumor cells, depending on the type of tumor cells, and, importantly, the composition of the extracellular matrix. Furthermore, this model allows direct observation of angiogenesis induced by the tumor–stroma interaction. Finally, reconstituting simultaneous angiogenesis and lymphangiogenesis induced by the tumor-stromal interaction with TME mimicking extrinsic factors is enabled. It is believed that the in vitro biomimetic model and the experimental concepts described will help to shed light on the complex biology of the TME.

A biomimetic tumor microenvironment model that mimics simultaneous angiogenesis and lymphangiogenesis toward tumor mass is created in microfluidic platform. Tumor–stromal mixture induces natural morphogenesis of endothelial cells to migrate through 3D fibrin matrix and interacts directly with the tumor cells. This model can potentially be used not only in drug evaluation but also in studying complex tumor microenvironment systematically.

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