Glycosylation of Cancer Extracellular Vesicles: Capture Strategies, Functional Roles and Potential Clinical Applications

Martins, Álvaro M; Ramos, Cátia C; Freitas, Daniela; Reis, Celso A.

doi:10.3390/cells10010109

Cited by 71 publications

(69 citation statements)

References 218 publications

(183 reference statements)

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“…We suggest that differential glycosylation analysis of EV-bound AT could help to explain the significantly increased risk for thromboembolism, predominantly in the venous circulation, that affects T2 patients. It has been evidenced previously that EV glycosylation can help to discriminate between healthy and pathological samples, and specific EV glycoconjugates are potential cancer biomarkers 56 .…”

Section: Discussionmentioning

confidence: 99%

Active antithrombin glycoforms are selectively physiosorbed on plasma extracellular vesicles

Radeghieri

Alacqua

Zendrini

et al. 2021

Preprint

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AT is a glycoprotein produced by the liver and acts as the most important antagonist of clotting factors. A deficit in AT production or function leads to coagulation disorders. Two kinds of AT deficiencies are reported, named quantitative (or type I) and qualitative (or type II) defects. The first is characterized by low levels of AT in the bloodstream, the latter by impaired AT activity related to dysfunctional domains of AT and it is challenging to diagnose. Although being a soluble protein, evidence of AT transported by plasma EVs has been found but the physicochemical features of the association of AT to EVs are missing. We separated and characterized EVs from the plasma of healthy subjects, focusing on AT association. We found AT is localized on the external leaflet of the EV membrane. Furthermore, 2D-electrophoresis conducted on plasma and EVs of healthy subjects highlighted that specific AT glycoforms are selectively enriched onto the EVs with respect to whole plasma, suggesting that glycosylation plays a role in the partitioning of AT between the EV surface and liquid plasma phase, and ultimately on the EV exofacial topology. Finally, we separated EVs from the plasma of 8 patients affected by type II AT defect. The comparison of the AT 2D-electrophoretic pattern of patients and healthy subjects highlighted a difference in AT adsorption onto EV surface, supporting the role of EVs in coagulation and suggesting a promising approach to improve diagnosis and management of type II AT deficiencies.

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Section: Discussionmentioning

confidence: 99%

Active antithrombin glycoforms are selectively physiosorbed on plasma extracellular vesicles

Radeghieri

Alacqua

Zendrini

et al. 2021

Preprint

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“…Glycosylation is the reaction in which a carbohydrate (oligosaccharide) is attached to a biomolecule. The EV membrane consists of abundant glycoproteins and surface glycosylation of urinary EVs was reported to demonstrate disease-specific modifications [ 26 ]. Lately, a significant level of glycoproteins was identified in the EVs of breast cancer patients [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Detection of Prostate Cancer via IR Spectroscopic Analysis of Urinary Extracellular Vesicles: A Pilot Study

et al. 2021

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Extracellular vesicles (EVs) are membranous nanoparticles naturally released from living cells which can be found in all types of body fluids. Recent studies found that cancer cells secreted EVs containing the unique set of biomolecules, which give rise to a distinctive absorbance spectrum representing its cancer type. In this study, we aimed to detect the medium EVs (200–300 nm) from the urine of prostate cancer patients using Fourier transform infrared (FTIR) spectroscopy and determine their association with cancer progression. EVs extracted from 53 urine samples from patients suspected of prostate cancer were analyzed and their FTIR spectra were preprocessed for analysis. Characterization of morphology, particle size and marker proteins confirmed that EVs were successfully isolated from urine samples. Principal component analysis (PCA) of the EV’s spectra showed the model could discriminate prostate cancer with a sensitivity of 59% and a specificity of 81%. The area under curve (AUC) of FTIR PCA model for prostate cancer detection in the cases with 4–20 ng/mL PSA was 0.7, while the AUC for PSA alone was 0.437, suggesting the analysis of urinary EVs described in this study may offer a novel strategy for the development of a noninvasive additional test for prostate cancer screening.

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“…Their surface recalls the characteristic of parental cell [7]: EXO membrane exposes lipids (cholesterol, ceramide, phosphatidylserine and sphingomyelin), proteins (antigen presenter, adhesion and transmembrane proteins), and multiple relevant saccharide components (Table 1), like high mannose, poly N-acetyllactosamine, α-2,6 sialic acid, and complex N-linked glycan, signature common to different cell type-derived EXOs. Glycans are relevant in the sorting of glycoproteins to MVs and the glycan profile is annoverated in many different studies as the necessary equipment involved in the EXO composition, release, targeting and uptake [42][43][44][45]. N-linked glycans have been also identified as determinants of protein trafficking into EXOs [46].…”

Section: Glycan Role In Exosome Biologymentioning

confidence: 99%

From Exosome Glycobiology to Exosome Glycotechnology, the Role of Natural Occurring Polysaccharides

2021

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Exosomes (EXOs) are nano-sized informative shuttles acting as endogenous mediators of cell-to-cell communication. Their innate ability to target specific cells and deliver functional cargo is recently claimed as a promising theranostic strategy. The glycan profile, actively involved in the EXO biogenesis, release, sorting and function, is highly cell type-specific and frequently altered in pathological conditions. Therefore, the modulation of EXO glyco-composition has recently been considered an attractive tool in the design of novel therapeutics. In addition to the available approaches involving conventional glyco-engineering, soft technology is becoming more and more attractive for better exploiting EXO glycan tasks and optimizing EXO delivery platforms. This review, first, explores the main functions of EXO glycans and associates the potential implications of the reported new findings across the nanomedicine applications. The state-of-the-art of the last decade concerning the role of natural polysaccharides—as targeting molecules and in 3D soft structure manufacture matrices—is then analysed and highlighted, as an advancing EXO biofunction toolkit. The promising results, integrating the biopolymers area to the EXO-based bio-nanofabrication and bio-nanotechnology field, lay the foundation for further investigation and offer a new perspective in drug delivery and personalized medicine progress.

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Glycosylation of Cancer Extracellular Vesicles: Capture Strategies, Functional Roles and Potential Clinical Applications

Cited by 71 publications

References 218 publications

Active antithrombin glycoforms are selectively physiosorbed on plasma extracellular vesicles

Active antithrombin glycoforms are selectively physiosorbed on plasma extracellular vesicles

Detection of Prostate Cancer via IR Spectroscopic Analysis of Urinary Extracellular Vesicles: A Pilot Study

From Exosome Glycobiology to Exosome Glycotechnology, the Role of Natural Occurring Polysaccharides

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