Abstract
Simple SummaryIntensive research in the field of cancer biology has discovered a unique mode of interplay between cells via extracellular bioactive vesicles called exosomes. Exosomes serve as intermediators among cells via their cargoes that, in turn, contribute in the progression of cancer. They are ubiquitously present in all body fluids as they are secreted from both normal and tumor cells. These minuscules exhibit multiple unique properties that facilitate their migration to distant locations and modulate the microenvironment for progression of cancer. This review summarizes the multifarious role of exosomes in various aspects of cancer research with its pros and cons. It discusses biogenesis of exosomes, their functional role in cancer metastasis, both protumorigenic and antitumorigenic, and also their applications in anticancer therapy.Exosomes, the endosome-derived bilayered extracellular nanovesicles with their contribution in many aspects of cancer biology, have become one of the prime foci of research. Exosomes derived from various cells carry cargoes similar to their originator cells and their mode of generation is different compared to other extracellular vesicles. This review has tried to cover all aspects of exosome biogenesis, including cargo, Rab-dependent and Rab-independent secretion of endosomes and exosomal internalization. The bioactive molecules of the tumor-derived exosomes, by virtue of their ubiquitous presence and small size, can migrate to distal parts and propagate oncogenic signaling and epigenetic regulation, modulate tumor microenvironment and facilitate immune escape, tumor progression and drug resistance responsible for cancer progression. Strategies improvised against tumor-derived exosomes include suppression of exosome uptake, modulation of exosomal cargo and removal of exosomes. Apart from the protumorigenic role, exosomal cargoes have been selectively manipulated for diagnosis, immune therapy, vaccine development, RNA therapy, stem cell therapy, drug delivery and reversal of chemoresistance against cancer. However, several challenges, including in-depth knowledge of exosome biogenesis and protein sorting, perfect and pure isolation of exosomes, large-scale production, better loading efficiency, and targeted delivery of exosomes, have to be confronted before the successful implementation of exosomes becomes possible for the diagnosis and therapy of cancer.
Highlights
Exosomes are bilayered endosomal nanovesicles, first discovered in 1983, as transferrin conjugated vesicles (50 nm) released by reticulocytes [1]
Due to the increasing interest of scientists in exosome biology, a consensus guideline was proposed by board members of International Society of Extracellular Vesicles under “minimal experimental requirements for definition of extracellular vesicles and their functions” (MISEV2014) which was later updated in 2018 (MISEV2018)
dendritic cells (DCs) and other antigen presenting cells (APCs) derived exosomes are loaded with specific drugs; miRNAs of interest or even exosomes alone are implemented to trigger immune response in the recipient individuals (Figure 4)
Summary
Exosomes are bilayered endosomal nanovesicles, first discovered in 1983, as transferrin conjugated vesicles (50 nm) released by reticulocytes [1]. Exosomes regulate physiological functions, such as neuronal communication, immune responses, reproductive activity, cell proliferation homeostasis, maturation and cellular waste disposition. They contribute in clinical disorders, including inflammation, cancer, cardiovascular diseases, neuronal pathologies and pathogenic infections [5]. The inexplicable nature of exosomes has raised concern about their role in the invasion and metastasis of cancer cells, encompassing epithelial-to-mesenchymal transition (EMT), angiogenesis, and immune regulation [12]. Instead of reviewing the isolated impact of exosomes, e.g., evasion of immune surveillance [13] for cancer progression, we have tried to encompass exosome-mediated propagation of oncogenic signaling, epigenetic regulation, modulation of tumor microenvironment (TME) and immune escape, EMT, angiogenesis, metastasis and drug resistance. Instead of perceiving specific therapeutic potential of exosomes, the present review has tried to decipher the entire repertoire of exosomes, including both protumorigenic and antitumorigenic impact
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