Macrophage and Triple-Negative Breast Cancer Cell Phenotype Changes in a 3D Co-Culture Model

Unraveling intricate cell-cell interactions in the tumor microenvironment (TME) remains challenging, especially when using a standardized 3D culture system. This study used the TNBC cell line, MDA-MB-231, and polarized M1-like or M2-like macrophages derived from THP-1 monocytes to establish 3D co-culture spheroids for mimicking the TME environment.

Drug efficacy, epithelial-mesenchymal transition (EMT) in cancer cells, macrophage phenotypes, and RNA sequencing of spheroids were performed. We observed that M2 macrophages increased the viability and proliferation rate of MDA-MB-231 cells in the 3D spheroids, while both M1 and M2 macrophages increased the chemosensitivity of MDA-MB-231 cells to doxorubicin and paclitaxel. Interestingly, instead of maintaining their phenotypes, M1 and M2 macrophages lost some polarization when 3D co-cultured with MDA-MB-231 cells.