Macrophage Polarization in Inflammatory Diseases

Liu, Yan-Cun; Zou, Xian-Biao; Chai, Yan-Fen; Yao, Yong-Ming

TAMs vary in distinct phenotypes in the different stages of tumors. Previous data showed an M1-like role for TAM in the initiation and promotion of tumors with the activation of NF-κB signal pathway [71] . In liver tumors, macrophages (known as Kupffer cells) engulf and kill circulating tumor cells in an M1-like manner, and the depletion of Kupffer cells in rats enhances metastasis [72] . However, TAM is transformed into M2-like phenotype in the development of tumors, and NF-κB signal pathway is down-regulated [73] . During the stage of invasion and migration, TAM is converted into M2 phenotype upon the stimulation of IL-4 secreted by CD4 + T cells and tumor cells, and functions as the key to the gate of invasion of tumor cells [74] . Mechanistically, TAM migrates and synthesizes epidermal growth factor (EGF) under the stimulation of colony-stimulating factor (CSF)-1 secreted by tumor cells, in turn activating the migration of tumor cells [75] . More interestingly, TAM and tumor cells migrate in lock-step, and both migration and chemotaxis of them could be inhibited by either the EGF or CSF-1 signaling pathways [64] . Matrix metalloproteinases 2 and matrix metalloproteinases 9 secreted by TAM could impair the matrix, and help tumor cells escape from the basement membrane, which is another important regulator of invasion of tumor cells [76] . In a word, the distinct phenotypes of macrophages regulate the activity of tumor cells in the different stages of tumors, which provide an attractive target for the treatment in the future.