Phenotypic Characteristics of Macrophages and Tumor Cells in Coculture

Abstract

Immunosuppressive activity of a tumor is provided by constituents of its microenvironment (TME), immune cells, particularly macrophages, which, instead of protecting the organism, render cancer cells more aggressive and metastatically active. A solid tumor is a spacious structure; a naive macrophage, on its way through the tumor, encounters newer cell populations; and its functioning can be improved. In our study, we employed the method of sequential cocultivation of monocyte-like THP-1 cells with A431 human epidermoid cancer cells and explored the changes in the behavior of both cell counterparts depending on cocultivation stage, cytokine profiles, and metalloproteinase 2 and 9 (MMP) activity. We found that the first contact of the monocyte with tumor cells already increased the tumor cell proliferation and migration, release of protumorigenic cytokines, and monocyte polarization into M2 phenotype. One of the most abundant cytokines induced by the cocultivation was tumor necrosis factor, TNF-alpha, a potent inducer of apoptosis. Its release led to the massive death of THP-1 cells, so that at the other stages of cocultivation, a weakened population of macrophages could not affect the behavior of tumor cells. In conclusion, the macrophage function in TME strongly depends on its cytokine content and the data reported here elucidate one scenario of interaction between stromal and cancer cells in a real tumor.