Macrophage differentiation and molecular mechanism in tumor microenvironment
Lingjia Hong, Manami Tanaka, Masato Yasui, Mariko Hara-Chikuma
Department of Pharmacology, School of Medicine, Keio University,160-8582, JAPAN
Macrophages regulate the innate immune system and maintain tissue homeostasis. In the tumor microenvironment, tumor-associated macrophages (TAMs) are found to promote tumor progression in several ways such as immune escape, angiogenesis, increased proliferation, and metastasis of cancer cells. In a solid tumor microenvironment, TAMs are thought to originate mostly from circulating monocytes; however, the molecular mechanism of monocyte differentiation into TAM remains unclear.
In this study, we aimed to determine intracellular signals or target molecules involved in TAM differentiation and explore novel therapy targeting it. We used THP-1 human monocyte cell line that is a useful tool to study macrophage in vitro. First, THP-1 cells were incubated with a conditional culture medium (CM) of different breast cancer cells (MDA-MB231, MDA-MB453, and MCF7). Among these cell lines, RT-PCR analysis demonstrated that the CM of MDA-MB231 increased the expressions of TAM markers, including CD163, CD206, CCL2, and MMP9, suggesting that THP-1 cells were polarized into TAM. Then, we determined whether TAM could promote the proliferation of MDA-MB231 breast cells. MDA-MB231 cells were incubated with TAM-derived CM, and cell proliferation was examined. We found that TAM-derived CM significantly promoted the growth of MDA-MB231 breast cells. Then, we explored the compound that inhibited the differentiation of monocytes into TAM by taking TAM markers as indicators. Further studies will show that some compounds modulate TAM differentiation.