Detection and proteomic characterization of extracellular vesicles in human pancreatic juice

Osteikoetxea, Xabier; Benke, Márton; Rodríguez, Marta; Pálóczi, Krisztina; Sódar, Barbara; Szvicsek, Zsuzsanna; Szabó-Taylor, Katalin; Vukman, Krisztina V.; Kittel, Ágnes; Wiener, Zoltán; Vékey, Károly; Harsányi, László; Szücs, Ákos; Turiák, Lilla; Buzás, Edit I.

doi:10.1016/j.bbrc.2018.03.107

Cited by 41 publications

(40 citation statements)

References 35 publications

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“…As carriers of disease‐associated molecules that can be found in biofluids, EVs have great potential as a noninvasive source of biomarkers for diseases such as cancer. Recently three groups (Hwang, Buzás, and Xiao) have performed comparative proteomic analysis on EVs from disease‐associated biofluids . Proteomic analysis of EVs from biofluids has been shown to decrease the background signal derived from highly abundant proteins, such as creatine in urine, resulting in greater sensitivity .…”

Section: Proteomic Profiling Of Evs In Clinical Samplesmentioning

confidence: 94%

“…For example, a large number of EV proteins isolated from urine specimens of bladder cancer patients were not identified by proteomics perfomed on straight urine without EV isolation . In line with this, a large number of EV proteins isolated from pancreatic juice of patients with chronic pancreatitis or pancreatic cancer were not identified when proteomics was performed on pancreatic juice without EV isolation . In both cases, the number of proteins that were identified only in the EV samples were ≥40%.…”

Section: Proteomic Profiling Of Evs In Clinical Samplesmentioning

confidence: 96%

“…In addition, different EV classes seem to contain distinct cargo. For instance, in the study from Buzás group, mucin‐5AC and mucin‐6 were uniquely identified in l‐EVs, while mucin‐16 and dihydropyrimidinase‐related protein 2 were exclusive to s‐EVs isolated from the pancreatic juice of pancreatic cancer patients . Similarly, the study from Xiao lab showed that BPIFA1 and CRNN were significantly enriched in l‐EVs, while MUC5B and IQGAP were enriched in s‐EVs from the saliva of lung cancer patients compared to healthy donors.…”

Section: Proteomic Profiling Of Evs In Clinical Samplesmentioning

confidence: 96%

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Protein Composition Reflects Extracellular Vesicle Heterogeneity

et al. 2019

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Extracellular vesicles (EVs) are membrane‐enclosed particles that are released by virtually all cells from all living organisms. EVs shuttle biologically active cargo including protein, RNA, and DNA between cells. When shed by cancer cells, they function as potent intercellular messangers with important functional consequences. Cells produce a diverse spectrum of EVs, spanning from small vesicles of 40–150 nm in diameter, to large vesicles up to 10 μm in diameter. While this diversity was initially considered to be purely based on size, it is becoming evident that different classes of EVs, and different populations within one EV class may harbor distinct molecular cargo and play specific functions. Furthermore, there are considerable cell type‐dependent differences in the cargo and function of shed EVs. This review focuses on the most recent proteomic studies that have attempted to capture the EV heterogeneity by directly comparing the protein composition of different EV classes and EV populations derived from the same cell source. Recent studies comparing protein composition of the same EV class(es) derived from different cell types are also summarized. Emerging approaches to study EV heterogeneity and their important implications for future studies are also discussed.

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Section: Proteomic Profiling Of Evs In Clinical Samplesmentioning

confidence: 94%

Section: Proteomic Profiling Of Evs In Clinical Samplesmentioning

confidence: 96%

Section: Proteomic Profiling Of Evs In Clinical Samplesmentioning

confidence: 96%

See 1 more Smart Citation

Protein Composition Reflects Extracellular Vesicle Heterogeneity

et al. 2019

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“…One such promising approach involves identification of secreted extracellular vesicles (EV) in the blood of patient to differentiate patients with PDAC from both patients who are disease-free or those with chronic pancreatitis (benign conditions). Several studies have attempted to identify EV associated protein using conventional cell lines in culture with further validation using blood samples from PDAC patients and healthy controls (4,(22)(23)(24). It is not clear whether organoid cultures can be used to discover new, clinically significant, secreted biomarkers.…”

Section: Organoids As Discovery Platform For Blood-based Biomarkers Imentioning

confidence: 99%

Pancreatic tumor organoids for modeling in vivo drug response and discovering clinically-actionable biomarkers

Huang

Bockorny

Paul

et al. 2019

Preprint

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Patient-derived models are transforming translational cancer research. It is not clear if the emergence of patientderived organoid (PDO) models can extend the utility of the widely used patient-derived xenograft (PDX). In addition, the utility of PDO models for serum biomarker discovery is not known. Here, we demonstrate that PDO models recapitulate the genomics, cell biology, glycomics and drug responses observed in PDX models. Furthermore, we demonstrate the applicability of PDO models for identification of N-glycans that are enriched in the glycome of pancreatic ductal adenocarcinoma (PDAC). Surprisingly, among all the glycans observed in PDX and PDOs, a core set of 57 N-glycans represent 50-94% of the relative abundance of all N-glycans detected, suggesting that only a subset of glycans dominate the cell surface landscape in PDAC. In addition, we outline a tumor organoid-based pipeline to identify surface proteins in extracellular vesicles (EV) from media supernatant of PDO cultures. When combined with the affinity-based validation platform, the EV surface proteins discovered in PDOs are effective in differentiating patients with PDAC from those with benign pancreatitis in the clinic, identifying PDO as powerful discovery platform for serum biomarkers. Thus, PDOs extend the utility of the archival collections of PDX models for translational research and function as a powerful platform for identification of clinically-actionable biomarkers in patients blood. Significance statement:Tumor organoids extend the utility of PDX models as platforms for investigating drug response, glycosylation changes and function as new platforms for discovering blood-based biomarkers

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“…Previous studies have identified glypican‐1 (GPC1), different types of mucins, the multidrug resistance protein 1 (MDR1) and the cystic fibrosis transmembrane conductance regulator (CFTR) in these vesicles, highlighting the potential of exosomes as circulating markers of pancreatic cancer . Further, pancreatic cancer exosomes have been shown to target and modulate pre‐metastatic niche formation in the liver through macrophage migration inhibitory factor (MIF), initiating profound phenotypic changes in the liver to coordinate metastasis .…”

Section: Introductionmentioning

confidence: 99%

Oncogenic and Non‐Malignant Pancreatic Exosome Cargo Reveal Distinct Expression of Oncogenic and Prognostic Factors Involved in Tumor Invasion and Metastasis

et al. 2019

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Exosomes are small extracellular membrane vesicles important in intercellular communication, with their oncogenic cargo attributed to tumor progression and pre‐metastatic niche formation. To gain an insight into key differences in oncogenic composition of exosomes, human non‐malignant epithelial and pancreatic cancer cell models and purified and characterized resultant exosome populations are utilized. Proteomic analysis reveals the selective enrichment of known exosome markers and signaling proteins in comparison to parental cells. Importantly, valuable insights into oncogenic exosomes (362 unique proteins in comparison to non‐malignant exosomes) of key metastatic regulatory factors and signaling molecules fundamental to pancreatic cancer progression (KRAS, CD44, EGFR) are provided. It is reported that oncogenic exosomes contain factors known to regulate the pre‐metastatic niche (S100A4, F3, ITGβ5, ANXA1), clinically‐relevant proteins which correlate with poor prognosis (CLDN1, MUC1) as well as protein networks involved in various cancer hallmarks including proliferation (CLU, CAV1), invasion (PODXL, ITGA3), metastasis (LAMP1, ST14) and immune surveillance escape (B2M). The presence of these factors in oncogenic exosomes offers an understanding of select differences in exosome composition during tumorigenesis, potential components as prognostic and diagnostic biomarkers in pancreatic cancer, and highlights the role of exosomes in mediating crosstalk between tumor and stromal cells.

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Detection and proteomic characterization of extracellular vesicles in human pancreatic juice

Abstract: Together our data show that detection and characterization of EVs directly in pancreatic juice is feasible and may prove to be a valuable source of potential biomarkers of pancreatic cancer.

Cited by 41 publications

References 35 publications

Protein Composition Reflects Extracellular Vesicle Heterogeneity

Protein Composition Reflects Extracellular Vesicle Heterogeneity

Pancreatic tumor organoids for modeling in vivo drug response and discovering clinically-actionable biomarkers

Oncogenic and Non‐Malignant Pancreatic Exosome Cargo Reveal Distinct Expression of Oncogenic and Prognostic Factors Involved in Tumor Invasion and Metastasis

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