Abstract

Extracellular Vesicles (EVs) are emerging as pivotal elements in cancer. Many studies have focused on the role of Small- (S)-EVs but in recent years Large-(L)-EVs have progressively gained increasing interest due to their peculiar content and functions. Tumor-derived L-EVs carry a lot of oncogenic proteins, nucleic acids and lipids to recipient cells and are involved in the reshaping of the tumor microenvironment as well as in the metabolic rewiring and the promotion of the pro-metastatic attitude of cancer cells. Several techniques have been developed for the isolation of L-EVs and commercial kits are also available for efficient and easy recovery of these vesicles. Also, the improvement in DNA sequencing and “omics sciences” profoundly changed the way to analyze and explore the molecular content of L-EVs, thus providing novel and potentially useful cancer biomarkers. Herein, we review the most recent findings concerning the role of L-EVs in cancer and discuss their possible use in oncology as “liquid biopsy” tools as compared to the other classes of EVs.

Highlights

  • Extracellular Vesicles (EVs) are emerging as important intercellular messengers regulating tumor progression and cell metabolism

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  • A similar mechanism could be used by cancer cells, since it has been demonstrated that a 12-HETE receptor, namely the BLT2, is implicated in cancer cell transformation, invasion and metastasis [24,25], as well as vascular endothelial growth factor (VEGF)-mediated angiogenesis [26]

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Summary

Introduction

Extracellular Vesicles (EVs) are emerging as important intercellular messengers regulating tumor progression and cell metabolism. Suitable yields of S-EVs for downstream analyses still require large volumes of biological fluids, limiting the applicability of exosomes as a high-throughput diagnostic tool due to high costs and analytical time. Their role is not completely understood, L-EVs have progressively gained increasing interest in the last years. L-EVs have been proposed to be involved in cancer metabolic rewiring [5], as well as in chemotherapy resistance [6] Their particular composition and easiness of recovery from any biological fluid make them a promising alternative to S-EVs, as a circulating diagnostic tool for molecular analyses. We summarize the main characteristics of EVs with a particular focus on L-EVs and discuss their involvement in cancer progression, as well as their possible applications in oncology

Nomenclature of Extracellular Vesicles
Biogenesis of L-EVs
Nucleic Acids
Proteins
Lipids
Methods for the Isolation of L-EVs
Ultracentrifugation
Ultrafiltration
Precipitation
Immune Affinity Interaction
EV Markers for Quality Control
Role of L-EVs in Cancer
L-EVs and Drug Resistance
Applications of L-EVs for Liquid Biopsy
Diagnosis and Prognosis
Predictive Biomarker
Conclusions and Future Perspectives
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