Cancer stem cell–derived exosomes: what is known to date

Cancer is one of the largest contributors to global morbidity and mortality. A significant effort has been undertaken to understand cancer pathophysiology to improve disease outcomes. Cancer stem cells (CSCs) are a self-renewing and differentiating subpopulation of tumor cells. Tumor metastasis, immune suppression, angiogenesis, resistance to treatment, and disease resurgence are some of the common cancer-related phenomena enabled by CSCs. Endosomal vesicles (EnVs), microvesicles (MVs), and apoptotic bodies play an important role in mediating cellular communication for disease progression. CSCs rely on EnVs and MVs to permit transformation to a stem-like profile and increase tumor heterogeneity. CSC-derived EVs carry proteins, lipids, and nucleic acids that alter the gene expression and function of the target cell. The growth factors, miRNAs, and long noncoding RNAs released by the CSCs alter the tumor microenvironment for tumor permissiveness. Epithelial-to-mesenchymal transition, heterotrophic adhesion, and extracellular matrix remodeling allow angiogenesis and metastasis of the tumor cells. EVs also mediate a protumor immune profile necessary for immune suppression, and evasion of targeting of the tumor by the immune cells. This allows metastasis and tumor cell infiltration. EVs released by CSCs enable the tumor cells to acquire slow cycling and quiescent state essential for refractory tumor phenotype. Further, EVs also mediate tumor heterogeneity and alter the expression of drug transporters reducing the efficacy of cancer treatment. Targeting CSCs using engineered EVs is a promising avenue for cancer therapy. EVs carrying nucleic acids, drugs, inhibitors, and antibodies have been demonstrated as a potential strategy for targeting CSCs.