Monocytes educated by cancer-associated fibroblasts secrete exosomal miR-181a to activate AKT signaling in breast cancer cells

Abstract

Significance Cancer-associated fibroblasts (CAFs), as a major component of tumor stroma, affect tumor cell behavior in different manners. Even though it has been shown that CAFs support tumor growth, not much is known about how they contribute to immunosuppression in the tumor microenvironment (TME) of breast cancer (BC). Tumor stromal cells may secrete paracrine factors, which can affect the distinct layers of the neoplastic population, resulting in phenotypic and signaling pathway alterations throughout the tumor cohort. CAFs take a crucial part in shaping the tumor immunosuppressive microenvironment in BC by recruiting monocytes and affecting their polarization states. Our findings propose that exosomal transfer of miR-18a1 may be a novel mechanism underlying the paracrine effects of tumor-educated monocytes and may provide a way for exosomes to promote tumor progression within the microenvironment of BC cells.

Keywords

• Breast cancer
• Cancer-associated fibroblasts
• Tumor-associated macrophages
• Immunosuppressive tumor microenvironment
• Exosomes
• AKT signaling