Determination of variability due to biological and technical variation in urinary extracellular vesicles as a crucial step in biomarker discovery studies

Oeyen, Eline; Willems, Hanny; Kindt, Ruben 't; Sandra, Koen; Boonen, Kurt; Hoekx, Lucien; Wachter, Stefan De; Ameye, Filip; Mertens, Inge

doi:10.1080/20013078.2019.1676035

Cited by 27 publications

(28 citation statements)

References 41 publications

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“…The inadequacy of uterine receptivity significantly contributes to failure during in vitro fertilization and embryo transplantation [50]. Increasing evidence indicates that sEVs miRNAs are potential biomarkers for the diagnosis and treatment of diseases [23,51,52]. In our study, miR-34c-5p, miR-210, and miR-30b were upregulated in sEVs during implantation.…”

Section: Discussionsupporting

confidence: 49%

MicroRNAs in Small Extracellular Vesicles Indicate Successful Embryo Implantation during Early Pregnancy

Tan

Shi

Liang

et al. 2020

Cells

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Synchronous communication between the developing embryo and the receptive endometrium is crucial for embryo implantation. Thus, uterine receptivity evaluation is vital in managing recurrent implantation failure (RIF). The potential roles of small extracellular vesicle (sEV) miRNAs in pregnancy have been widely studied. However, the systematic study of sEVs derived from endometrium and its cargos during the implantation stage have not yet been reported. In this study, we isolated endometrium-derived sEVs from the mouse endometrium on D2 (pre-receptive phase), D4 (receptive phase), and D5 (implantation) of pregnancy. Herein, we reveal that multivesicular bodies (MVBs) in the endometrium increase in number during the window of implantation (WOI). Moreover, our findings indicate that CD63, a well-known sEV marker, is expressed in the luminal and glandular epithelium of mouse endometrium. The sEV miRNA expression profiles indicated that miR-34c-5p, miR-210, miR-369-5p, miR-30b, and miR-582-5p are enriched during WOI. Further, we integrated the RIF’s database analysis results and found out that miR-34c-5p regulates growth arrest specific 1 (GAS1) for normal embryo implantation. Notably, miR-34c-5p is downregulated during implantation but upregulated in sEVs. An implication of this is the possibility that sEVs miR-34c-5p could be used to evaluate uterine states. In conclusion, these findings suggest that the endometrium derived-sEV miRNAs are potential biomarkers in determining the appropriate period for embryo implantation. This study also has several important implications for future practice, including therapy of infertility.

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Section: Discussionsupporting

confidence: 49%

MicroRNAs in Small Extracellular Vesicles Indicate Successful Embryo Implantation during Early Pregnancy

Tan

Shi

Liang

et al. 2020

Cells

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“…Facing this bottleneck issue, several authors have pursued other approaches for isolating highly pure EVs from urine samples. In this regard, several two-step combination methods (e.g., UF combined with SEC or asymmetrical-flow field-flow fractionation) have been pursued to minimize the impact of urine contaminants on the purity of isolated EV sample [ 165 , 169 , 170 , 171 ]. Unfortunately, despite having higher EV recovery yields (up to 60%) these techniques fail to provide the same reliable EV proteomic analysis obtained via gUC gold standard [ 165 , 171 ].…”

Section: Extracellular Vesicles From Liquid Biopsies As a Source Omentioning

confidence: 99%

Urinary Biomarkers in Bladder Cancer: Where Do We Stand and Potential Role of Extracellular Vesicles

Oliveira

Caires

Oliveira

et al. 2020

Cancers

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Extracellular vesicles (EVs) are small membrane vesicles released by all cells and involved in intercellular communication. Importantly, EVs cargo includes nucleic acids, lipids, and proteins constantly transferred between different cell types, contributing to autocrine and paracrine signaling. In recent years, they have been shown to play vital roles, not only in normal biological functions, but also in pathological conditions, such as cancer. In the multistep process of cancer progression, EVs act at different levels, from stimulation of neoplastic transformation, proliferation, promotion of angiogenesis, migration, invasion, and formation of metastatic niches in distant organs, to immune escape and therapy resistance. Moreover, as products of their parental cells, reflecting their genetic signatures and phenotypes, EVs hold great promise as diagnostic and prognostic biomarkers. Importantly, their potential to overcome the current limitations or the present diagnostic procedures has created interest in bladder cancer (BCa). Indeed, cystoscopy is an invasive and costly technique, whereas cytology has poor sensitivity for early staged and low-grade disease. Several urine-based biomarkers for BCa were found to overcome these limitations. Here, we review their potential advantages and downfalls. In addition, recent literature on the potential of EVs to improve BCa management was reviewed and discussed.

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“…This also holds true for high invasive MDA-MB-231 vs. low invasive MCF7 cell lines [238,239]. Although in general terms, inter-patient variability seems to be in line with that of other biomarkers [240], a biomarker-based pilot study to assess normal levels of EV-shuttled factors is crucial for most biomarkers (e.g., miRNAs), since the field is new, and normality ranges, biological variability and technical variability are still not established [241,242]. However, the fact that these are communication devices for cells, opens many possibilities in the drug delivery field.…”

Section: Discussionmentioning

confidence: 99%

Switching Homes: How Cancer Moves to Bone

Ponzetti

Rucci

2020

IJMS

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Bone metastases (BM) are a very common complication of the most prevalent human cancers. BM are extremely painful and may be life-threatening when associated with hypercalcaemia. BM can lead to kidney failure and cardiac arrhythmias and arrest, but why and how do cancer cells decide to “switch homes” and move to bone? In this review, we will present what answers science has provided so far, with focus on the molecular mechanisms and cellular aspects of well-established findings, such as the concept of “vicious cycle” and “osteolytic” vs. “osteosclerotic” bone metastases; as well as on novel concepts, such as cellular dormancy and extracellular vesicles. At the molecular level, we will focus on hypoxia-associated factors and angiogenesis, the Wnt pathway, parathyroid hormone-related peptide (PTHrP) and chemokines. At the supramolecular/cellular level, we will discuss tumour dormancy, id est the mechanisms through which a small contingent of tumour cells coming from the primary site may be kept dormant in the endosteal niche for many years. Finally, we will present a potential role for the multimolecular mediators known as extracellular vesicles in determining bone-tropism and establishing a premetastatic niche by influencing the bone microenvironment.

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Determination of variability due to biological and technical variation in urinary extracellular vesicles as a crucial step in biomarker discovery studies

Cited by 27 publications

References 41 publications

MicroRNAs in Small Extracellular Vesicles Indicate Successful Embryo Implantation during Early Pregnancy

MicroRNAs in Small Extracellular Vesicles Indicate Successful Embryo Implantation during Early Pregnancy

Urinary Biomarkers in Bladder Cancer: Where Do We Stand and Potential Role of Extracellular Vesicles

Switching Homes: How Cancer Moves to Bone

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