关键词: 肿瘤微环境, 乳腺癌, 乳酸, 巨噬细胞

Abstract: Objective To investigate that lactic acid regulates polarization of phenotype and function of macrophages in tumor microenvironment. Methods Balb/c mice were inoculated by 4T1 breast tumor cells with the mammary gland injection.The tumor tissues were harvested at different time points and detected the lactic acid concentration. The expression of M1 and M2 markers in RAW264.7 cells treated with different concentration of lactic acid were detected by RT-PCR ,FACS and Western Blot. The mouse cytokine array chip was used to evaluate the release of cytokines from RAW cells treated with 15mmol/L lactic acid. Phagocytosis and antigen presenting function was evaluated by using FACS. Results lactic acid concentration of mouse breast tumor was higher than that of normal breast tissue（P<0.05）. M2 markers of RAW cells were up-regulated and M1 markers were down-regulated by 15mmol/L lactic acid（P<0.05）.M1 cytokines secretion of RAW cells treated with 15mmol/L lactic acid was down-regulated（P<0.05）. Phosphorylated NFκB P65 was down-regulated by 15mmol/L lactic acid（P<0.05）.The phagocytosis was not affected by lactic acid, but the expression of the antigen presenting and co-stimulatory molecules were down-regulated in RAW cells treated with 15mmol/L lactic acid（P<0.05）. Conclusion lactic acid induces the M2 phenotype shift and inhibits the antigen presenting function of RAW cells. NFκB P50/P65 are involved in the phenotype polarization of macrophages.This study suggested that lactic acid plays a indispensable role in macrophages polarization in tumor microenvironment.

Key words: tumor microenvironment, breast tumor, lactic acid, macrophages