The role of exosomes in metastasis and progression of melanoma

Gowda, Raghavendra; Robertson, Bailey M.; Iyer, Soumya; Barry, John Mitchell; Dinavahi, Saketh S.; Robertson, Gavin P.

doi:10.1016/j.ctrv.2020.101975

Cited by 72 publications

(60 citation statements)

References 150 publications

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“…Probably brand new technological solutions, such as an integrated microfluidic exosome analysis platform, will become powerful non-invasive diagnostic tools for easy screening and monitoring of the EV-based Liquid biopsy (143). There are expectations that EVs will be a promising tool for transfer of the drugs and vector signals to the target cells to regulate many processes involved in myocardium and vasculature reparation, endothelial homoeostasis, and adaptations to myocardial injury (144). These advances have made EV-based point-of-care applications possible and promising, while new devices for use in liquid biopsy need to be developed in the future.…”

Section: Future Directions and Challenges In Ev Researchmentioning

confidence: 99%

Extracellular Endothelial Cell-Derived Vesicles: Emerging Role in Cardiac and Vascular Remodeling in Heart Failure

Berezin

2020

Front. Cardiovasc. Med.

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Extracellular vesicles play a pivotal role in numerous physiological (immune response, cell-to-cell cooperation, angiogenesis) and pathological (reparation, inflammation, thrombosis/coagulation, atherosclerosis, endothelial dysfunction) processes. The development of heart failure is strongly associated with endothelial dysfunction, microvascular inflammation, alteration in tissue repair, and cardiac and vascular remodeling. It has been postulated that activated endothelial cell-derived vesicles are not just transfer forms of several active molecules (such as regulatory peptides, coagulation factors, growth factors, active molecules, hormones that are embedded onto angiogenesis, tissue reparation, proliferation, and even prevention from ischemia/hypoxia), but are instead involved in direct myocardial and vascular damage due to regulation of epigenetic responses of the tissue. These responses are controlled by several factors, such as micro-RNAs, that are transferred inside extracellular vesicles from mother cells to acceptor cells and are transductors of epigenetic signals. Finally, it is not a uniform opinion whether different phenotypes of heart failure are the result of altered cardiac and vascular reparation due to certain epigenetic responses, which are yielded by co-morbidities, such as diabetes mellitus and obesity. The aim of the review is to summarize knowledge regarding the role of various types of extracellular endothelial cell-derived vesicles in the regulation of cardiac and vascular remodeling in heart failure.

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Section: Future Directions and Challenges In Ev Researchmentioning

confidence: 99%

Extracellular Endothelial Cell-Derived Vesicles: Emerging Role in Cardiac and Vascular Remodeling in Heart Failure

Berezin

2020

Front. Cardiovasc. Med.

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“…Due to the protection of the lipid bilayer, exosomes are relatively stable. The proteins and other molecules enclosed within these small vesicles are protected from degradation (21,22). These characteristics make exosomes great sources of non-invasive biomarkers or therapeutic targets for cancers.…”

Section: Introductionmentioning

confidence: 99%

Proteomic Profiling of Serum Exosomes From Patients With Metastatic Gastric Cancer

et al. 2020

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Background: Clinical management of metastatic gastric cancer (mGC) remains a major challenge due to a lack of specific biomarkers and effective therapeutic targets. Recently, accumulating evidence has suggested that exosomes play an essential role in cancer metastasis and can be an excellent reservoir of novel biomarkers and candidate therapeutic targets for cancer. Therefore, in this study, we aimed to reveal the proteomic profile of mGC-derived exosomes. Methods: Exosomes were isolated from pooled serum samples of 20 mGC patients and 40 healthy controls (HC) by ultracentrifugation. Next, quantitative proteomic analyses were applied to analyze the protein profiles of the exosomes, and bioinformatic analyses were conducted on the proteomic data. Finally, the expression of exosomal protein candidates was selectively validated in individual subjects by western blot analysis. Results: We isolated exosomes from serum samples. The size of the serum derived exosomes ranged from 30 to 150 nm in diameter. The exosomal markers CD9 and CD81 were observed in the serum exosomes. However, the exosomal negative marker calnexin, an endoplasmic reticulum protein, was not detected in exosomes. Overall, 443 exosomal proteins, including 110 differentially expressed proteins (DEPs) were identified by quantitative proteomics analyses. The bioinformatics analyses indicated that the upregulated proteins were enriched in the process of protein metabolic, whereas the downregulated proteins were largely involved in cell-cell adhesion organization. Surprisingly, 10 highly vital proteins (UBA52,

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“…Metastatic melanoma lacks robust prognostic biomarkers, which could translate into adequate therapeutic interventions and survival benefits for patients. Nonetheless, several interesting reports have tried to define the role of circulating miRNAs in melanoma progression, even though the different detection and normalization methods used prevent the identification of a definite miRNA signature for the early detection of melanoma [26][27][28][29].…”

Section: Discussionmentioning

confidence: 99%

Circulating miRNAs in Small Extracellular Vesicles Secreted by a Human Melanoma Xenograft in Mouse Brains

Guglielmi

Nardella

Musa

et al. 2020

Cancers

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The identification of liquid biomarkers remains a major challenge to improve the diagnosis of melanoma patients with brain metastases. Circulating miRNAs packaged into tumor-secreted small extracellular vesicles (sEVs) contribute to tumor progression. To investigate the release of tumor-secreted miRNAs by brain metastasis, we developed a xenograft model where human metastatic melanoma cells were injected intracranially in nude mice. The comprehensive profiles of both free miRNAs and those packaged in sEVs secreted by the melanoma cells in the plasma demonstrated that most (80%) of the sEV-associated miRNAs were also present in serum EVs from a cohort of metastatic melanomas, included in a publicly available dataset. Remarkably, among them, we found three miRNAs (miR-224-5p, miR-130a-3p and miR-21-5p) in sEVs showing a trend of upregulation during melanoma progression. Our model is proven to be valuable for identifying miRNAs in EVs that are unequivocally secreted by melanoma cells in the brain and could be associated to disease progression.

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The role of exosomes in metastasis and progression of melanoma

Cited by 72 publications

References 150 publications

Extracellular Endothelial Cell-Derived Vesicles: Emerging Role in Cardiac and Vascular Remodeling in Heart Failure

Extracellular Endothelial Cell-Derived Vesicles: Emerging Role in Cardiac and Vascular Remodeling in Heart Failure

Proteomic Profiling of Serum Exosomes From Patients With Metastatic Gastric Cancer

Circulating miRNAs in Small Extracellular Vesicles Secreted by a Human Melanoma Xenograft in Mouse Brains

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