Extracellular vesicle-mediated transport of non-coding RNAs between stem cells and cancer cells: implications in tumor progression and therapeutic resistance

Recent years have witnessed intensive progress in studying extracellular vesicles (EVs), both for understanding their basic biology and contribution to variety of diseases, biomarker discovery, and their potential as gene delivery vectors and source of innovative therapies. As such, stem cell-derived EVs have contributed significant knowledge which led to the development of cell-free therapies in regenerative medicine. Although, the role of stem cell-derived EVs in maintaining stemness, differentiation and repairing tissue injuries is relatively well-understood; however, knowledge about the contribution of stem cell-derived EVs in cancer progression is just emerging. The aim of this review is, therefore, to discuss the recent developments in stem cell-derived EVs and tumor progression, placing a particular focus on non-coding RNA (ncRNA) mediated cancer progression and resistance against therapies. This includes the failure of normal hematopoiesis and the progression of myeloid neoplasms, enhanced capacity of cancer cells to proliferate and metastasize, and the conversion of normal cells into cancer cells, activation of angiogenic pathways and dormancy in cancer cells. These processes are shared by mesenchymal stem cells (MSCs), cancer stem like-cells and cancer cells in an intricate intratumoral network in order to create self-strengthening tumor niche. In this context, EV-ncRNAs serve as mediators to relay bystander effects of secreting cancer stem cells (CSCs) into recipient cells for priming a tumor permissive environment and relaying therapeutic resistance. Collectively, this knowledge will improve our understandings and approaches in finding new therapeutic targets in the context of CSCs, which could be benefited through engineering EVs for innovative therapies.