Abstract
Cancer is one of the most important health problems and the second leading cause of death worldwide. Despite the advances in oncology, cancer heterogeneity remains challenging to therapeutics. This is because the exosome-mediated crosstalk between cancer and non-cancer cells within the tumor microenvironment (TME) contributes to the acquisition of all hallmarks of cancer and leads to the formation of cancer stem cells (CSCs), which exhibit resistance to a range of anticancer drugs. Thus, this review aims to summarize the role of TME-derived exosomes in cancer biology and explore the clinical potential of mesenchymal stem-cell-derived exosomes as a cancer treatment, discussing future prospects of cell-free therapy for cancer treatment and challenges to be overcome.
Highlights
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The discovery of the role of these exosomes in cancer biology has allowed us to understand the complexity of the tumor microenvironment (TME); on the other hand, it has allowed us to explore the biotechnological potential of mesenchymal stem cell (MSC)-derived exosomes as therapeutics for cancer treatment in a novel therapeutic approach known as cell-free therapy
Based on the cumulative evidence supporting the view that these cancer-derived exosomes contribute to all carcinogenesis steps [26,47,48,49,50], this review aims to summarize the role of cancer-derived exosomes in cancer initiation, promotion, progression, and metastasis, highlighting mechanisms of action commonly reported in different malignancies
Summary
Exosomes contain selective repertoires of proteins, nucleic acids (RNAs), lipids, and metabolites that regulate signaling pathways in the recipient cells [33]. ESCRT-III is considered to be required for the scission of the ILVs into the MVE lumen [36], studies have reported the presence of ILVs within the lumen of MVBs in the ESCRT-depleted cells, indicating that ESCRT-independent pathways for ILV formation exist [37,38]. In this sense, recent evidence supports an alternative pathway for sorting exosomal cargo into MVBs in an ESCRT-independent manner, which seems to depend on raft-based microdomains for the lateral segregation of cargo within the endosomal membrane [22,37]. By exhibiting sorting mechanisms, which select the proteins and RNAs that will compose the exosome content, it is expected that exosomes derived from non-cancer cells and cancer cells possess distinct activities in both physiology and pathophysiology
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