M1 Macrophage-Derived Exosomes Convert TAMs into an Anti-Tumor M1 Phenotype to Inhibit the Progression of Prostate Cancer

Abstract

Background: Prostate cancer is the most common and solid malignancy among male tumors worldwide. Converting tumor-associated macrophages (TAMs) into anti-tumor M1 macrophages holds a promising potential for cancer treatment. Therefore, this study investigated whether M1 macrophage-derived exosomes affect prostate cancer progression by inducing TAM reprogramming into M1-like macrophages. Methods: LPS-induced RAW264.7 cells were polarized into M1-type macrophages. Exosomes isolated from the M1 macrophages (M1-exos) were observed using transmission electron microscopy (TEM), tracked by nanoparticle tracking analysis (NTA), and identified through western blot analysis. After this, M1-exos were co-cultured with human prostate cancer (PC-3) cells and interleukin-4 (IL-4)-induced M2-like macrophages. The effects of M1-exos on prostate cancer progression and TAM polarization were evaluated using cell counting kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), flow cytometry, Transwell, and wound healing assays. Furthermore, to analyze the impact of M1-exos on prostate cancer progression by inducing TAM polarization, in vivo xenograft tumor models were constructed, followed by H&E staining, immunohistochemistry, and TdT-mediated dUTP nick end labeling (TUNEL) assays. Results: We successfully polarized immature M0 macrophages into an M1 phenotype using RAW264.7 cells and obtained M1-exos from these cells. Moreover, findings from both in vivo and in vitro experiments unveiled that M1-exos inhibited the proliferation (p < 0.05), invasion (p < 0.05), and migration of prostate cancer cells (p < 0.05). Additionally, M1-exos promoted apoptosis (p < 0.05) and induced the polarization of TAM into M1-type macrophages. Conclusion: M1-exos induced the polarization of TAM into the M1 phenotype with anti-tumor potential, thereby suppressing prostate cancer growth and metastasis. Therefore, M1-exos hold promising potential for treating prostate cancer.