Exosomes and Cell Communication: From Tumour-Derived Exosomes and Their Role in Tumour Progression to the Use of Exosomal Cargo for Cancer Treatment

Abstract

Exosomes are nano-vesicle-shaped particles secreted by various cells, including cancer cells. Recently, the interest in exosomes among cancer researchers has grown enormously for their many potential roles, and many studies have focused on the bioactive molecules that they export as exosomal cargo. These molecules can function as biomarkers in diagnosis or play a relevant role in modulating the immune system and in promoting apoptosis, cancer development and progression. Others, considering exosomes potentially helpful for cancer treatment, have started to investigate them in experimental therapeutic trials. In this review, first, the biogenesis of exosomes and their main characteristics was briefly described. Then, the capability of tumour-derived exosomes and oncosomes in tumour microenvironments (TMEs) remodelling and pre-metastatic niche formation, as well as their interference with the immune system during cancer development, was examined. Finally, the potential role of exosomes for cancer therapy was discussed. Particularly, in addition, their use as carriers of natural substances and drugs with anticancer properties or carriers of boron neutron capture therapy (BNCT) and anticancer vaccines for immunotherapy, exosomes as biological reprogrammers of cancer cells have gained increased consensus. The principal aspects and the rationale of this intriguing therapeutic proposal are briefly considered.

Keywords: cancer; exosomal cancer cells reprogramming; exosomal cancer evolution; exosomal cancer therapy; exosomes; oncosomes.

Figure 1

Biogenesis of exosomes. (A) Endocytosis begins at the cytoplasmic membrane. Early endosomes (EEs) form by the fusion of uncoated endocytic vesicles. EEs either return to the plasma membrane (recycling endosome) or convert into late endosomes/multivesicular bodies (LEs/MVBs). Protein sorting of ILVs (intraluminal vesicles) occurs through endosomal sorting complexes required for transport (ESCRT) dependent or independent mechanism. ESCRT 0, ESCRT I, ESCRT II, ESCRT III are four components of ESCRT machinery that ubiquitinate the substrates on the part of the inward budding endosomal membrane. ILVs are ready to be degraded by lysosome or rescued by de-ubiquitinating enzymes (DUBs) through Rab GTPases (Rab27A and Rab27B) which allow the MVBs to move to the cell periphery. Finally MVBs through the SNARE complex fuse with the plasma membrane and lead to exocytosis (release of ILVs as exosomes to the extracellular space). Extracellular protein; Receptor; Lipid; RNA. (B) Ectosomes derive from the plasma membrane by direct gemmation. Large oncosomes, as microvesicles originate from plasma membrane [8]. Exosomes are derived and secreted through a “classical” pathway. ER = endoplasmic reticulum. Microvesicle; Apoptotic bodies; Exosome; Exomere; Oncosome.