Signal regulatory protein a associated with the progression of oral leukoplakia and oral squamous cell carcinoma regulates phenotype switch of macrophages

Signal regulatory protein a (SIRPa) is a cell-surface protein expressed on macrophages that are regarded as an important component of the tumor microenvironment. The expression of SIRPa in oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC), and further explored the role of SIRPa on the phenotype, phagocytosis ability, migration, and invasion of macrophages in OSCC were investigated. The expression of SIRPa in OLK was higher than in OSCC, correlating with the expression of CD68 and CD163 on macrophages. After cultured with the conditioned media of oral cancer cells, the expression of SIRPa on THP-1 cells was decreased gradually. In co-culture system, macrophages were induced into M2 phenotype by oral cancer cells. Blockade of SIRPa inhibited phagocytosis ability and IL-6, TNF-a productions of macrophages. In addition, the proliferation, migration, and IL-10, TGF-beta productions of macrophages were upregulated after blockade of SIRPa. Macrophages upregulated the expression of SIRPa and phagocytosis ability, and inhibited the migration and invasion when the activation of NF-kB was inhibited by pyrrolidine dithiocarbamate ammonium (PDTC). Hence, SIRPa might play an important role in the progression of OLK and oral cancer, and could be a pivotal therapeutic target in OSCC by regulating the phenotype of macrophages via targeting NF-kB.