The study of extracellular vesicles (EVs) in cancer progression is a complex and rapidly evolving field. Whole categories of cellular interactions in cancer which were originally presumed to be due solely to soluble secreted molecules have now evolved to include membrane-enclosed extracellular vesicles (EVs), which include both exosomes and shed microvesicles (MVs), and can contain many of the same molecules as those secreted in soluble form but many different molecules as well. EVs released by cancer cells can transfer mRNA, miRNA, and proteins to different recipient cells within the tumor microenvironment, in both an autocrine and paracrine manner, causing a significant impact on signaling pathways, mRNA transcription, and protein expression. The transfer of EVs to target cells, in turn, supports cancer growth, immunosuppression, and metastasis formation.
Schematic of the numerous interactions between breast tumor-derived EVs and stromal, epithelial, and immune cells within the tumor niche and the resulting changes that enhance cancer growth and metastasis. Breast cancer cells avoid detection from the immune system through EV-mediated decrease in the cytotoxicity of NK and T-cells and secretion of proinflammatory cytokines from macrophages. Tumor EVs enter fibroblasts and stimulate proangiogenic ERK and AKT kinase activation. Concurrently, EVs cause the secretion of oncogenic cytokines TGFβ and VEGF in mesenchymal stem cells. Additionally, tumor EVs enter surrounding cancer cells to upregulate signaling pathways that promote growth and metastasis, including increases in coagulation, adhesion, and a decrease in levels of tumor suppressors. To promote invasion, EVs induce epithelial cells to secrete growth factors and cause destruction of endothelial vascular structures, thus enhancing tumor growth.