Abstract 3240: Prostate cancer exosomes and their effects on macrophage engulfment and polarization

Abstract

Abstract The purpose of this study is to explore the effects of prostate cancer-derived exosomes on macrophage engulfment and polarization. Exosomes are small vesicles secreted by virtually all cells, which contain nucleic acids, lipids, proteins, and carbohydrates. Exosomes can be abundantly found in cancer patient secretions (serum, urine, etc.) and contain a high amount of RNA molecules, some of them being miRNA, and parts of the DNA of the cell of origin. One of the functions of exosomes is to mediate cellular communication. This occurs as they are secreted from one cell and then distribute their contents into other cells. Some exosomes specifically target immune cells. The miRNA the exosomes carry can silence genes involved in the activation of these immune cells, leading to immune suppression and tumor growth. Macrophages are often found surrounding the tumor microenvironment, as they are recruited by tumor signals to promote angiogenesis and metastasis. These macrophages, which are often called tumor associated macrophages (TAMs), are exposed to various signals derived from the tumor microenvironment, including exosomes. Previous data generated in our lab suggests that the co-culture of macrophages with PC3 and DU145 cell lines results in a decrease in macrophage phagocytosis and an M2-like polarization state. For this study, we exposed U937 cells to phorbol 12-myristate 13-acetate (PMA) for 24 hours to allow for differentiation. Then, we co-cultured these macrophages with isolated exosomes from spent media from both PC3 and DU145 cell lines at 1, 2, 3, 4, 5, 6, 12, and 24 hours. We then allowed the macrophages to phagocytose fluorescent microbeads for 1 hour. Flow cytometry analysis of these macrophages revealed that the total bead phagocytosis starts decreasing at 3 hours of exosome co-culture compared to control. Interestingly, total bead phagocytosis resumes to normal at 12 and 24 hours of exosome co-culture. Gene expression analysis of these macrophages suggests an M2 phenotype from hours 2-24. These results suggest that prostate cancer-derived exosomes can target macrophages and affect their phagocytosis. Further research is required to elucidate the specific genes these exosomes target. Citation Format: Evita G. Weagel, Wei Meng, Richard A. Robison, Kim L. O’Neill. Prostate cancer exosomes and their effects on macrophage engulfment and polarization. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3240.