Abstract

Simple SummaryExtracellular vesicles (EVs) are extensively distributed in various biological fluids, and contain diverse bioactive molecules including proteins, nucleic acids and lipids. They are considered to provide high stability to the associated molecular cargoes because of encapsulation by the lipid bilayer, making them ideal for liquid biopsy and as a drug delivery system. Moreover, EVs can affect immunomodulatory functions, including antigen presentation and immune activation and suppression. Inhibiting the production of tumor-derived EVs can support tumor immunity, and immune cell-derived EVs can be used as an anticancer vaccine. This review summarizes the biological functions and isolation methods of EVs, and explores their diagnostic and therapeutic applications in lung cancer.Extracellular vesicles (EVs) are nano-sized lipid-bound particles containing proteins, nucleic acids and metabolites released by cells. They have been identified in body fluids including blood, saliva, sputum and pleural effusions. In tumors, EVs derived from cancer and immune cells mediate intercellular communication and exchange, and can affect immunomodulatory functions. In the context of lung cancer, emerging evidence implicates EV involvement during various stages of tumor development and progression, including angiogenesis, epithelial to mesenchymal transformation, immune system suppression, metastasis and drug resistance. Additionally, tumor-derived EVs (TDEs) have potential as a liquid biopsy source and as a means of therapeutic targeting, and there is considerable interest in developing clinical applications for EVs in these contexts. In this review, we consider the biogenesis, components, biological functions and isolation methods of EVs, and the implications for their clinical utility for diagnostic and therapeutic applications in lung cancer.

Highlights

  • Lung cancer is the worldwide leading cause of cancer-related mortality, resulting in an estimated 1.8 million deaths per year [1]

  • Because the majority of lung cancers are diagnosed at the advanced stages of disease, early detection is key for reducing mortality

  • Exosome secretion has been shown to require sphingolipid ceramide, with the release of exosomes attenuated after the depletion of neutral sphingomyelinase, which plays a crucial role in the sorting of proteolipid proteins into Intraluminal vesicle (ILV) [12]

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Summary

Introduction

Lung cancer is the worldwide leading cause of cancer-related mortality, resulting in an estimated 1.8 million deaths per year [1]. EVs have been implicated in intercellular communication and are known to modulate tumor–host immune interactions [3] Extracellular vesicles and their tumor-derived molecular cargoes have recently received considerable. 2 ofExtra cellular vesicles and their tumor-derived molecular cargoes have recently received considerable interest for liquid biopsy applications in early cancer detection. They are being applied for the diagnosis of other diseases, including virus and parasitic infections interest for liquid biopsy applications in early cancer detection. They are being ap[4,5]. EV isolation methods possible clinical utility for diagnostic and therapeutic applications are discussed

The Biogenesis of EVs
Biogenesis
The Roles of EVs in Lung Cancer
EV Isolation Methods in Clinical Practice
Microfluidics
EV-Associated Proteins
EV-Associated RNA
EV-Associated DNA
EV-Associated Lipids
Immune Cell Inhibitory Effect of EVs
Suppression of TDEs
Cancer Vaccine
Application of EVs as Drug Delivery Systems
Findings
Conclusions

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