Investigation of lung cancer cells-derived exosomes effects on macrophage polarization and functions

Lung cancer has the highest mortality rate in both men and women worldwide. With our developing technology and knowledge, the research of methods in cancer targeted treatments have turned to target such as tumor microenvironment, tumor-derived exosomes, tumor-associated macrophages. Exosomes are part of tumor microenvironment that promote tumorigenesis, progression, metastasis, treatment resistance and provide to communication between cells, via transfer their contents to other cells in tumor microenvironment. Considering that tumor microenvironment trains macrophages to transforms them into tumor-associated macrophage, which has M2 phenotype and promotes tumor progression, rather than M1 macrophage that has anti-tumor activity and induced by Toll Like Receptors or lipopolysaccharides, we aimed to investigate the effects of exosomes and TLR agonists in this process. In our study, isolated exosomes derived from A549 lung cancer cells and exosomes derived from stimulated A549 lung cancer cells with TLR4 agonist were stained with CD9 antibody and analyzed by flow cytometry. Effects of these exosomes, on macrophage polarization, phagocytosis activity and cell cycle in THP-1 monocytic cell line were investigated. Our results demonstrated that exosomes, which isolated from both conditions, change macrophage morphology and increase the adhesion and aggregation of cells. Also our results showed that exosomes derived from stimulated A549 lung cancer cells with TLR4 agonist, significantly decreased M2 phenotype transformation and created M1/M2 mixed population. In addition, exosomes derived from stimulated A549 lung cancer cells with TLR4 agonist, do not have significant effects on phagocytosis or cell cycle of THP-1 cell lines.