Large Extracellular Vesicles—A New Frontier of Liquid Biopsy in Oncology

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.

Extracellular Vesicles in Advanced Prostate Cancer: Tools to Predict and Thwart Therapeutic Resistance

“…LOs appear to be more promising for a future clinical use. With a diameter of 1 to 10 µm, they are 100 to 1000 times larger than exosomes and contain proteins, RNA and DNA [123]. Moreover, LOs have also been shown to be a subpopulation of EVs containing DNA with tumor-specific molecular content [122].…”

The Power of Extracellular Vesicles in Myeloproliferative Neoplasms: “Crafting” a Microenvironment That Matters

“…The International Society of Extracellular Vesicles have classified EVs into three main groups: (1) exosomes, small vesicles with diameters ≤100–150 nm that are formed inside multivesicular bodies; (2) microvesicles, medium size vesicles of plasma membrane origin ranging in diameters up to 1000 nm; and (3) apoptotic bodies, large vesicles with diameters > 1000 nm that are produced by cells undergoing apoptosis [ 55 ]. Consistently, based on diameter, biogenesis and cargo, different classes of EVs have been identified, including either Small (S)- or Large (L)-EVs [ 56 , 57 , 58 ]. Exosomes originate from the endosomal system with a progressive accumulation of intraluminal vesicles within large multivesicular bodies.…”

“…Although L-EVs have been less investigated as compared to S-EVs and their role is not completely understood, L-EVs have progressively gained increasing interest in the last years. Indeed, L-EVs have been shown in cancer including breast cancer, prostate cancer, glioblastoma, pancreatic cancer, colon cancer, melanoma and leukemia [ 56 ]. However, only large oncosomes (LO) have been described to be released exclusively by cancer cells.…”

Molecular insights and clinical impacts of extracellular vesicles in cancer

“…Thus, many publications use the term large EVs , which does not accurately reflect the LO sub-population. 60 , 61 …”