Avaliação das alterações fenotípicas induzidas pela lipoxina em macrófagos derivados de diferentes tipos de tumores

Abstract

The presence of inflammation in the tumor microenvironment is one of the hallmarks of cancer. Macrophages are immune response cells that act as modulators of inflammation, mediating different events in the inflammatory process. Because of their plasticity, they can assume different phenotypes depending on the type of stimulus and their microenvironment. In general, classically activated macrophages, or M1 macrophages, have a pro-inflammatory characteristic and production of ROS and NO, which are important for their anti-tumor profile. Alternately activated macrophages, or M2 macrophages, have anti-inflammatory properties, inducing tissue remodeling and repair. The tumor microenvironment is rich in macrophages, called TAM (tumor-associated macrophage), which have an M2 phenotype and are directly related to different stages of tumor development, modulating migration, invasion, angiogenesis and metastasis. Due to their high complexity and plasticity, therapies that focus on TAMs, particularly those that can change their profile and reprogram their functions against the tumor, are promising targets for cancer control. In previous research, our group demonstrated that lipoxin is able to modify the phenotype of TAMs, restoring their cytotoxic properties, such as the production of ROS and NO, leading to apoptosis of tumor cells. However, the work carried out so far has shown the effect of lipoxin on TAMs originating from only one tumor type, polarized with conditioned medium from MV3, a human melanoma cell line. Therefore, in this work, we aimed to analyze the effects of lipoxin on the phenotypic profile of tumor associated macrophages derived by different types of tumors. To obtain TAMs, macrophages derived from human monocytes were stimulated and differentiated to TAM with the conditioned medium of tumor cells MV3 (human melanoma cell line), MDAMB-231 and MCF-7 (breast cancer cell lines), U373 (glioblastoma cell line) and PC-3 (prostate cancer cell line). We saw that TAMs from different types of tumors are similar in terms of their phenotypic profile, assuming M2-like characteristics. We also showed that lipoxin was effective in TAMs polarized with MC from melanoma (MV3), breast cancer (MCF-7), glioblastoma (U373) and prostate cancer (PC-3), once this treatment induced a phenotypic switch between the M2 profile of TAMs to an M1 profile. Taken together, our data suggest that the different TAMs are similar in terms of their profile, and the lipoxin treatment proved to be effective in modulating the phenotype of TAMs originating from different types of tumors.