Evaluation of Cancer Cell Membrane Disruption Property of Poly(vinyl alcohol)-ursodeoxycholic acid by 3D Cancer-Stromal Models with Macrophages

Abstract text In three-dimensional (3D) cancer tissue models, the low solubility of type I collagen (Col I) is a limitation in reproducing cancer tissue with high collagen density. we previously reported a “sedimentation culture method” using collagen microfibers (CMF) homogenized Col I powder. This 3D cancer tissue model is expected to reproduce tumor microenvironment comparable to that in tumors bearing mice owing to its high collagen density. However, this 3D cancer tissue model including immune cells such as macrophages has not been reported. In this study, we fabricated a 3D culture system including normal human dermal fibroblasts, human umbilical vein endothelial cells, and cancer cells human monocytes cell line; THP-1 cells by sedimentation culture using CMF. 3D cancer tissue models co-cultured with human colorectal cancer cells for 5 days increased the expression levels of CD14 and CD206, markers of macrophages and M2 macrophages, in THP-1 cells, suggesting differentiation induction toward macrophages and polarization toward M2-like macrophages. We could also demonstrate the applicability of drug efficacy evaluation systems by evaluating the cytotoxicity of poly(vinyl alcohol)-ursodeoxycholic acid15 that induce cell death in response to weak acidic tumor microenvironment in 3D cancer tissue models with macrophages. This 3D cancer tissue models with macrophages are expected to be applied as tools for evaluating the efficacy of cancer therapeutic molecules and for understanding in detail the behavior of immune cells within the tumor microenvironment.