Effect of the murine melanoma tumor microenvironment metabolites on macrophages lipid metabolism modulation

Abstract

Macrophages (MAs) are cells widely distributed by tissues, participating in various biological processes. These cells play an important role in inflammation with the production of cytokines and lipid mediators. For the activation of MA, the presence of soluble factors in the cellular microenvironment is necessary, polarizing them in two distinct patterns: classical activation (M1) or alternative activation (M2). M1 are fundamental in the immune response against intracellular microorganisms and tumors. M2 are more heterogeneous, promoting tissue repair and remodeling, and also tumor progression. In cancer research, the identification of genetic and phenotypic changes in the cancer cells themselves may explain the nature of this disease. However, the analysis of the tumor microenvironment is of great importance for a better understanding of the development of cancer. The tumor microenvironment is very complex, with the presence of a large number of cells and cellular metabolites. Tumor Associated Macrophages (MATs) produce a unique microenvironment that influences both the tumor cell properties and modulates the activity of the MATs themselves, since these cells have diversity and functional plasticity. The lactic acid released by tumor cells in the microenvironment promotes the modulation of MA to express high amounts of VEGF-± and Arginase-I, which contribute to tumor growth. Thus, in this project we will investigate the influence of the metabolite of the tumor microenvironment on the activation of macrophages, correlating with the modulation of lipid droplets formation and eicosanoid production, which are important factors in the effective response to tumors. (AU)