Publication Summary:

Breast cancer is the leading cause of death in female cancer patients. There are no effective treatments once the tumors spread to other parts of the body, a process called metastasis. Macrophages are the most abundant immune cells in breast tumors, and contribute to tumor initiation, progression, and metastasis. Emodin has been found to exert anti-tumor effects through promoting cell cycle arrest and apoptosis, and inhibiting angiogenesis, but its effects on tumor-associated macrophages during cancer metastasis have not been investigated. In this study, mice were inoculated with breast cancer cells in mammary fat pads and subsequently treated with emodin after the primary tumors reached the size of a soybean. Tumor growth, lung metastasis, and macrophage infiltration in the lungs were analyzed. Cell culture experiments were performed to examine the effects of emodin on macrophage phenotype and migration. It was found that emodin significantly suppressed breast cancer lung metastasis in mice. Reduced infiltration of macrophages, particularly pro-tumor macrophages (called M2-like macrophages), in lungs was observed in emodin-treated mice. Cell culture experiments showed that emodin decreased the migration of macrophages toward tumor cell-conditioned medium and inhibited macrophage M2 polarization. Mechanistically, Emodin suppressed STAT6 phosphorylation and C/EBPβ expression, two crucial signaling events in macrophage M2 polarization, in macrophages. Taken together, this study, for the first time, demonstrated that emodin suppressed lung metastasis of breast tumors probably through inhibiting macrophage recruitment and M2 polarization in the lungs.

Previous

Emodin attenuates systemic and liver inflammation in hyperlipidemic mice administrated with lipopoly