Macrophage-mediated tumorigenic effects of breast cancer cell exosomes

Abstract

Purpose: As a heterogeneous disease, breast cancer is one of the most commonly diagnosed cancers due to hereditary/genetic factors and non-hereditary factors and is a leading cause of disease-associated death among women all over the world. Macrophages are one of the cell types that have essential roles in physiological and pathological cellular processes containing hemostasis, inflammation, and carcinogenesis. Exosomes secreted by cancer cells regulate cellular processes such as the polarization of macrophages, different organ metastasis, and drug resistance via internalized macrophages. In this study, we aimed to reveal the exosome-mediated regulation of the tumor microenvironment in specific to macrophage cells.Materials and Methods: THP-1 monocyte cells are cultured with RPMI-1640 medium supplemented with 20 ng/ul phorbol-12-myristate-13-acetate (PMA) for 48 hours to induce macrophage differentiation. Exosomes of MCF-10A and MDA-MB-231 cells were isolated using a commercial kit. Fold changes in proliferation capacities of MCF-10A treated with exosomes of MDA-MB-231 cells were calculated.Results: A statistically significant increase in the expression of genes involved in the inflammation-related JAK/STAT pathway in THP-1 cells treated with MDA-MB-231 exosomes was observed. Besides, we detected morphological and proliferative changes in MCF-10A cells that were co-cultured with THP-1/MDA-MB-231exo cells.Conclusion: This study may contribute to the literature by showing that phenotypic differences in immune system cells can occur through exosomes in the tumor microenvironment.