Transfer of miRNA in tumor-derived exosomes suppresses breast tumor cell invasion and migration by inducing M1 polarization in macrophages

Aims: Macrophage repolarization from M1 to M2 phenotype is one of the hallmarks of malignancy. M2 macrophages are the most represented population in the tumor microenvironment and play an active role in tumor progression. In recent years, microRNAs (miRNAs) have been identified as a regulator of macrophage polarization. Main methods: In this study, miR-130 was delivered to M2 macrophages using tumor-derived exosomes. Then, we evaluated the macrophage polarization status by assessment of specific markers and cytokines for M1 and M2 phenotype. The phagocytosis ability of macrophages was also investigated. Additionally, we performed migration and invasion assays to detect the effect of macrophage reprogramming on breast cancer cells migration and invasion. Key findings: The findings of the current study indicated that exosomes efficiently delivered miR-130 into macrophages. Delivery of miR-130 into macrophages resulted in upregulation of M1 specific markers and cytokines, including CD86, Irf5, Nos2, TNF-alpha, and IL-1 beta and downregulation of M2 specific markers and cytokines, including CD206, Ym1, Arg, TGF-beta, and IL-10. The phagocytosis ability of macrophages also enhanced after treatment with miRNA-loaded exosomes. Furthermore, migration and invasion assays demonstrated reduced ability of 4T1 breast cancer cells for migration and invasion after macrophages reprogramming. Significance: These observations suggest that repolarization of M2 macrophages to M1 phenotype using miRNAcontaining exosomes can be a therapeutic strategy against tumor invasion and metastasis in breast cancer.

Automated summary

The study demonstrated that repolarization of M2 macrophages to M1 phenotype using tumor-derived exosomes loaded with miR-130 led to a reduction in migration and invasion abilities of breast cancer cells. The findings suggest a therapeutic potential in targeting tumor invasion and metastasis in breast cancer through this approach.