Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-Protein Cargo Delineates Distinct Subpopulations of Cancer-Derived Extracellular Vesicles

ABSTRACT: Extracellular vesicles (EVs) are membrane-encapsulated particles that vary greatly in size and content. Although both normal and tumor cells produce an array of small EVs (S-EVs), only tumor cells have been found to release a population of atypically large EVs (L-EVs), also known as large oncosomes (LO). Little is known about the cargo of L-EVs, and how it differs from the S-EVs. Given the potential for tumor-derived L-EVs to provide insights into disease mechanisms and course, we performed proteomic analysis of L- and S-EVs derived from three cancer models followed by comparative proteomic and transcriptomic analysis of EVs from the prostate cancer model. 1) We identified both common and model-specific protein signatures for L- and S-EVs. 2) A subset of the proteins enriched in prostate cancer cell-derived L-EVs were also identified in L-EVs isolated from plasma of patients with metastatic prostate cancer. 3) Proteins enriched in L-EV that were also identified at the transcript level were mostly mitochondrial in origin, as confirmed by single vesicle RNA-Seq. Additionally, the L-EV mitochondrial signature was detected in plasma-derived L-EVs and distinguished patients with prostate cancer from cancer-free individuals as well as patients with metastatic prostate cancer from those with localized disease, corroborating the relevance of an integrative multi-analyte approach focused on L-EVs for liquid biopsy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE231846 | GEO | 2025/04/16

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Whole proteome and transcriptome analysis of cancer-derived EVs overlap in specific pathways and distinct EV population

Project description:Extracellular Vesicles (EVs) are particles of different sizes, covered by a lipid bilayer membrane and containing highly heterogeneous cargo. Cancer cell-derived EVs have been the main object of an extensive investigation in the field because they carry cancer-specific molecular cargo and can promote cancer progression. Cancer-derived EVs include populations of atypically large EVs (L-EVs), which have been referred to as tumor microvesicles, large oncosomes, or simply L-EVs. While small EVs (S-EVs), which include exosomes, have been investigated by a plethora of reports, little is known about L-EVs. The paucity of studies comparing protein cargo of L- and S-EVs and studies focusing on protein-coding RNA, and the absence of integrative analyses to compare the protein and gene expression in different EV fractions, prompted us to perform mass spectrometry to profile three different, size-based EV fractions generated by three cancer cell models (glioma, prostate and breast cancer). We identified protein signatures for L- and S-EVs either common to all cell types or specific to each of them individually. The proteins enriched in prostate cancer cell-derived L-EVs were also identified in L-EVs from patients with metastatic prostate cancer by a SWATH proteomic assay. We also performed RNA-Seq on the prostate cancer model and integrated proteomic and transcriptomic datasets. GSEA revealed that mitochondrial function was enriched in L-EVs versus S-EVs at both the RNA and protein level. The mitochondrial signature at the transcriptome level was confirmed by single cell RNA-Seq of L- EVs in vitro. The integrated L-EV proteomic and transcriptomic signature enabled distinction between benign and localized prostate cancer, as well as between localized cancer and metastatic castration-resistant cancer.

2025-04-22 | GSE214804 | GEO

Integration of the whole proteome and transcriptome reveals a strong correlation between the protein and mRNA in a distinct population of cancer-derived EVs

Project description:Extracellular vesicles (EVs) are particles of different sizes, covered by a lipid bilayer membrane and containing highly heterogeneous cargo. Cancer cell-derived EVs have been the main object of an extensive investigation in the field because they carry cancer-specific molecular cargo and can promote cancer progression. Cancer-derived EVs include populations of atypically large EVs (L-EVs) that can be pelleted by a low/medium speed centrifugation, which have been referred to as tumor microvesicles, large oncosomes, or simply L-EVs. While small EVs (S-EVs), which pellet at a high speed centrifugation and include exosomes, have been investigated by a plethora of reports, little is known about the cargo of L-EVs. The paucity of studies comparing protein cargo of L- and S-EVs, of studies focused on protein coding RNA, and the absence of integrative analyses to compare the protein and gene expression in different EV fractions, prompted us to perform mass spectrometry to profile three different, size-based EV fractions generated by three cancer cell models (glioma, prostate and breast cancer). We identified general as well as cancer type-specific protein signatures for L- and S-EVs. A subset of the proteins enriched in prostate cancer cell-derived L-EVs was also identified in L-EVs from plasma of patients with metastatic prostate cancer by an independent Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH) mass spectrometry analysis. Proteomic and transcriptomic analyses of the prostate cancer-derived EVs revealed an enrichment of mitochondrial functions in L-EVs versus S-EVs at both the protein and RNA level. The mitochondrial signature was confirmed in L-EVs by single EV RNA-Seq. The integrated L-EV proteomic and transcriptomic signature enabled distinction between benign and localized prostate cancer, as well as between localized cancer and metastatic castration-resistant cancer.

2025-04-16 | PXD038011 | Pride

Whole proteome and transcriptome analysis of cancer-derived extracellular vesicles overlap in specific pathways and distinct EV populations

Project description:Extracellular Vesicles (EVs) are particles of different sizes, covered by a lipid bilayer membrane and containing highly heterogeneous cargo. Cancer cell-derived EVs have been the main object of an extensive investigation in the field because they carry cancer-specific molecular cargo and can promote cancer progression. Cancer-derived EVs include populations of atypically large EVs (L-EVs), which have been referred to as tumor microvesicles, large oncosomes, or simply L-EVs. While small EVs (S-EVs), which include exosomes, have been investigated by a plethora of reports, little is known about L-EVs. The paucity of studies comparing protein cargo of L- and S-EVs, of studies focused on protein coding RNA, and the absence of integrative analyses to compare the protein and gene expression in different EV fractions, prompted us to perform mass spectrometry to profile three different, size-based EV fractions generated by three cancer cell models (glioma, prostate and breast cancer). We identified protein signatures for L- and S-EVs either common to all cell types or specific to each of them individually. The proteins enriched in prostate cancer cell-derived L-EVs were also identified in L-EVs from patients with metastatic prostate cancer by a SWATH proteomic assay. We also performed RNA-Seq on the prostate cancer model and integrated proteomic and transcriptomic datasets. GSEA revealed that mitochondrial function was enriched in L-EVs versus S-EVs at both the RNA and protein level. The mitochondrial signature at the transcriptome level was confirmed by single cell RNA-Seq of L- EVs in vitro. The integrated L-EV proteomic and transcriptomic signature enabled distinction between benign and localized prostate cancer, as well as between localized cancer and metastatic castration-resistant cancer.

2025-04-16 | PXD038518 | Pride

Quantitative proteomic analysis of large and small extracellular vesicles from prostate cancer cells

Project description:Extracellular vesicles (EVs) are membranous structures of variable size, shed from diverse cell types including highly invasive, fast migrating, amoeboid tumor cells. Silencing of the Diaphanous-related formin-3 (DIAPH3) protein in DU145 prostate cancer cells induces an amoeboid phenotype characterized by membrane blebbing and shedding of an atypically large population of EVs termed large oncosomes. We employed this cell system to characterize, for the first time, the global protein composition of large oncosomes and small EVs. The salient finding of this study, revealed by SILAC-based LC-MS/MS analysis was the identification of 20 unique proteins in large oncosomes and 7 in small EVs. Additionally, both types of EV were significantly enriched in proteins with cancer-related functions, suggesting that tumor interactions with the microenvironment are influenced by EV cargo. Proteins belonging to a series of functional classes, including GTPases, ESCRTs, RNA-binding proteins and membrane proteins, often identified in and which are sometimes considered specific for exosomes, appeared in both EV populations. Proteins such as CK18 and FN1, significantly enriched in large oncosomes, were selected to develop an assay to detect large oncosomes in the circulation. Finally, proteins over-represented in large oncosomes versus small EVs with at least a four-fold enrichment were significantly associated with cell migration, docetaxel resistance, angiogenesis, and prostate cancer bone metastasis, suggesting a distinct functional role in tumor progression for this larger class of EV. These observations indicate that, despite their origination from the same cell donors, the two distinct EV populations are enriched in different proteins and contribute diversified functions. These findings underscore the need for additional in-depth analyses to understand the unique contribution of subpopulations of EVs to tumor progression.

2015-03-18 | PXD000776 | Pride

Proteomic signatures of extracellular vesicles secreted by non-mineralizing and mineralizing human osteoblasts and stimulation of tumor cell growth

Project description:Beyond forming bone, osteoblasts play pivotal roles in various biological processes, including hematopoiesis and bone metastasis. Extracellular vesicles (EVs) have recently been implicated in intercellular communication via transfer of proteins and nucleic acids between cells. Here, we focused on the proteomic characterization of non-mineralizing (NMOBs) and mineralizing (MOBs) human osteoblast (SV-HFOs) EVs and investigated their effect on human prostate cancer (PC3) cells by microscopic, proteomic and gene expression analyses. Proteomic analysis showed that 97% of the proteins were shared among NMOB and MOB EVs, and 30% were novel osteoblast-specific EV proteins. Label-free quantification demonstrated mineralization stage-dependent five-fold enrichment of 59 and 451 EV proteins in NMOBs and MOBs, respectively. Interestingly, bioinformatic analyses of the osteoblast EV proteomes and EV-regulated prostate cancer gene expression profiles showed that they converged on pathways involved in cell survival and growth. This was verified by in vitro proliferation assays where osteoblast EV uptake led to two-fold increase in PC3 cell growth compared to cell-free culture medium-derived vesicle controls. Our findings elucidate the mineralization stage-specific protein content of osteoblast-secreted EVs, show a novel way by which osteoblasts communicate with prostate cancer, and open up innovative avenues for therapeutic intervention. PC3 cells were treated with extracellular vesicles from non-mineralizing and mineralizing SV-HFOs for three different incubation times (4hrs, 24hrs, 48hr)

2014-10-28 | E-GEOD-56172 | biostudies-arrayexpress

Proteomic signatures of extracellular vesicles secreted by non-mineralizing and mineralizing human osteoblasts and stimulation of tumor cell growth

2014-10-28 | GSE56172 | GEO

Circulating tumor extracellular vesicles to monitor metastatic prostate cancer genomic and transcriptomic evolution

Project description:Extracellular vesicles (EVs) secreted by tumors are abundant in plasma, but their potential for multi-omic profiling remains widely unexplored. Here, we pursued next-generation sequencing of circulating EV-DNA and EV-RNA in metastatic prostate cancer (mPC), using a range of in-vitro and in-vivo models, validating our findings in 35 mPC patients with longitudinal samples collected during androgen receptor signaling inhibitor (ARSI) therapy. EV-DNA copy-number (CN) profiles matched same-patient biopsies and ctDNA (p<0.001) and EV-DNA tumor fraction (TF) associated with shorter time to progression. We developed a novel approach for studying mRNA in circulating EVs (RExCuE), showing high correlation between EV-RNA and tumor biopsies (r>0.7, p<0.001). EV-RNAseq signatures at 4 weeks of therapy associated with clinical responses. Last, we derived a specific signature of ARSI response in EV-RNA in vivo that predicted response to therapy. In conclusion, EV profiling enables the study of mPC evolution at transcriptomics level in liquid biopsies.

2024-06-30 | GSE221709 | GEO

A reductionist approach using primary and metastatic cell-derived extracellular vesicles reveals hub proteins associated with oral cancer prognosis

Project description:Oral squamous cell carcinoma (OSCC) has high mortality rates that are largely associated with lymph node metastasis. However, the molecular mechanisms that drive OSCC metastasis are unknown. Extracellular vesicles (EVs) are membrane-bound particles that play a role in intercellular communication and impact cancer development and progression. Thus, profiling EVs would be of great significance to decipher the role of EV cargo in OSCC metastasis. For that purpose, we used a reductionist approach to map the proteomic, miRNA, metabolomic, and lipidomic profiles of extracellular vesicles (EVs) derived from human primary tumor (SCC-9) cells and matched lymph node metastases (LN1) cells. Distinct omics profiles were associated with the metastatic phenotype, including 670 proteins, 217 miRNAs, 26 metabolites, and 64 lipids differentially abundant between LN1- and SCC-9-derived EVs. A multi-omics integration identified 11 ‘hub proteins’ significantly decreased at the metastatic site compared to primary tumor-derived EVs. We confirmed the validity of these findings with analysis of data from multiple public databases, and found that low abundance of seven hub proteins in metastatic EVs is correlated with reduced survival and tumor aggressiveness in cancer patients. In summary, this multi-omics approach identified proteins transported by EVs that are associated with metastasis, and which may potentially serve as prognostic markers in OSCC.

2021-04-26 | ST001755 | MetabolomicsWorkbench

RNA-Seq of Tissue, Plasma and Urinary Extracellular Vesicles of Prostate Cancer patients

Project description:We performed RNA-Seq analysis of plasma and urinary EVs collected before and after radical prostatectomy, and matched tumor and normal prostate tissues of 10 patients with prostate cancer. To identify putative cancer-derived RNA biomarkers, we searched for RNAs that were overexpressed in tumor as compared to normal tissues, present in the pre-operation EVs and decreased in the post-operation EVs in each RNA biotype.

2022-11-16 | E-MTAB-11910 | biostudies-arrayexpress

Effects of prostate cancer patient urinary extracellular vesicles and hypoxic extracellular vesicles from prostate cancer cell lines on the transcriptomes of cancer-associated and normal fibroblasts

Project description:Patient-derived prostate fibroblast primary cultures PCF-54 and PCF-55 were established from two specimens of PC tissues. Urinary EVs were isolated from urine samples of 3 patients with PC and 2 healthy males and used for the treatment of prostate fibroblast primary cultures and normal foreskin fibroblasts. Normoxic and hypoxic EVs were isolated from cell culture medium of PC3 and LNCaP prostate cancer cell lines, cultivated in normoxic and hypoxic conditions respectively. The EV-treated fibroblasts were subjected to RNA sequencing analysis.

2023-04-01 | E-MTAB-11317 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data