EVALUATION OF PHENOTYPIC CHANGES INDUCED BY LIPOXIN IN MACROPHAGES DERIVED FROM BREAST CANCER

INTRODUCTION AND OBJECTIVES: Macrophages are immune cells that act as modulators of inflammation and can assume different phenotypes depending on the stimulus. Generally, M1 macrophages have pro-inflammatory characteristics, with increased expression of the CD86 marker, reactive oxygen species (ROS), and nitric oxide (NO), which are important for anti-tumoral effects. Alternatively activated macrophages, or M2 macrophages, have anti-inflammatory properties, with high expression of the CD206 marker and are involved in tissue repair. In breast cancer research carried out focused only on the tumor cell.  However, the tumor microenvironment (TME) plays a central role in tumor progression. In this context, tumor-associated macrophages (TAMs) are highlighted as highly plastic cells within the TME with M2 properties are directly related to different stages of tumor development. Our group demonstrated that lipoxin, a pro-resolving lipid mediatior, triggered M2 profile of TAM to an M1-like phenotype, restoring their cytotoxic properties, leading to apoptosis of MV3, a human melanoma cell line. The effects of lipoxin on TAMs derived from other types of tumor have not been demonstrated. Therefore, in this work, we aimed to analyze the effects of lipoxinon the phenotypic profile of TAM in the context of breast cancer MATERIAL AND METHODS: To obtain TAMs, macrophages derived from human monocytes were stimulated and differentiated to TAM with the conditioned medium (CM) from breast cell lines MDAMB-231 and MCF-7 for 72h. After this period, we conduced lipoxin treatment (10nM) for an additional 72h.  RESULTS AND CONCLUSION: We observed that TAMs from breast cancers exhibited a similar phenotypic profile, assuming M2-like characteristics with high expression of CD206. We also demonstrated that lipoxin was effective in TAMs polarized with CM from MCF-7 and MDAMB-231, once this treatment induced a phenotypic switch between the M2 profile of TAMs to an M1 profile. This switch led to high expression of ROS, NO, and CD86, resulting in increased phagocytosis by TAMs.  Additionaly, we found that CM of lipoxin- treated TAMs reduced the migration of MCF-7 but did not affected the migration of MDAMB-231. Taken together, our data suggested that lipoxin is effective in modulating the phenotype of TAMs in the context of breast cancer, making it a promising therapeutic target.