Facile construction of tumour spheroids with induced M2 macrophage polarization for anticancer drug screening

Abstract Tumour-associated macrophages (TAMs) are involved in cancer progression and drug resistance in the tumour microenvironment (TME). Consequently, macrophages as therapeutic targets have garnered increased attention; however, there are hurdles to screening interactions between cancer and macrophages owing to technical difficulties in recapitulating in vitro physiological systems. In this study, we propose a simple strategy to construct tumour spheroids with induced M2 macrophage polarization for anticancer drug screening. We observed that cytokine expression related to the TME in three-dimensional (3D) cancer spheroids was enhanced compared with that in two-dimensional conventional cancer cell cultures. We also demonstrated that the 3D breast tumour spheroids promote M2-like TAM polarization via granulocyte–macrophage colony-stimulating factor and granulocyte colony-stimulating factor. Furthermore, adipose tissue-derived stem cells, an abundant stromal cell population in the breast cancer TME, further enhanced the M2 phenotype in the in vitro tumour spheroids. Therefore, we propose the tumour spheroids as a drug screening platform to evaluate drug efficacy in cancers. Overall, the simple strategy to form tumour spheroids developed in this study will broaden the understanding of communication between cancer cells and macrophages and contribute to the evaluation of cancers and the development of better strategies for their therapy and management.