Investigation of the effects of M1-M2 induced macrophages and macrophage-derived exosomes on pre/post-tumorigenic processes of breast cancer spheroids

In this thesis, it was aimed to examine the effects of various nanoparticles and their different doses on macrophage polarization and also to evaluate the pre/post-tumorigenic effects of macrophage-derived exosomes. First of all, the polarization types were determined by examining the gene expression and cytokine release by macrophage cells (Raw264.7) induced by seven different nanoparticles. Palladium nanoparticles (PdNP) which were selected based on the nanoparticle screening results affect the metastatic, epithelial-mesenchymal transition (EMT), apoptotic and invasive properties compared with the control groups M0, M1, and M2 macrophages in breast cancer (MCF-7) tumor micro-tissues by co-culture systems. Following, an in vitro wound-healing experiment was performed to analyze the effect of exosomes obtained from macrophages with different phenotypes (M0, M1, M2, and PdNP-induced) on the invasive properties of MCF-7. Eventually, the exosomes drug resistance effect to 5-Fluorouracil (5-FU) in tumor micro-tissues was also evaluated. In line with the results obtained, PdNP-induced macrophages and PdNP-induced macrophage exosomes (PdNP-Exo) suppress metastasis, and EMT-related genes in breast tumor micro-tissues were determined which provided an increase in apoptotic genes expression. To put it in a nutshell, this research predicted that PdNP-Exos can be promising natural immunomodulatory vesicles and also support cancer-fighting platforms.