Study of the Reciprocal Interaction Between Tumor Cells and Macrophages Based on the Biomimic Microfluidic Device

Tumor-macrophage interactions play a key role in various physiological and pathological processes, such as angiogenesis, immune suppression, and extracellular matrix remodeling. In this study, a biomimetic microfluidic chip was developed to simulate the immune microenvironment of glioma through the co-culture of glioma cells and macrophages in a three-dimensional (3D) matrix. Glioma cells were embedded in collagen I solution after forming spheroids in the microwell array chip and subsequently co-cultured with macrophages in different channels. This chip enabled the real-time monitoring of morphological changes in macrophages, the invasion of glioma cell spheroids, and molecular interactions between different cell types. Two distinct cell types could be extracted and isolated in situ for subsequent molecular biological detection, such as Western blotting or qPCR. The results demonstrated that glioma cell spheroids significantly enhanced invasiveness in the presence of macrophages. Moreover, the phenotype of macrophages altered from M0 to M2 (tumor-supportive) under the influence of tumor cells. The molecular mechanism mediating this reciprocal process was extensively explored. It is believed that this 3D microfluidic tumor model could serve as a useful tool for studying the biological properties of the glioma microenvironment. In addition, a more comprehensive understanding of the mechanisms involved in glioma metastasis could be obtained, especially of how tumor inflammatory cells, including tumor-associated macrophages (TAM), affect invasion process.