Dataset Information

CD99 modulates the proteomic landscape of Ewing sarcoma cells and related-extracellular vesicles.

ABSTRACT: Ewing sarcoma (EWS) is an aggressive pediatric bone tumor characterized by unmet clinical needs and an incompletely understood epigenetic heterogeneity. Here we considered CD99, a major surface molecule hallmark of EWS malignancy. Fluctuations of CD99 expression strongly impair cell dissemination, differentiation, and death. CD99 is also loaded within extracellular vesicles (EVs) and the delivery of CD99 positive or CD99 negative EVs dynamically exerts oncogenic or oncosuppressive functions to recipient cells, respectively. We undertook mass spectrometry and functional annotation analysis to investigate the consequences of CD99 silencing on the proteomic landscape of EWS cells and related EVs. Our data demonstrate that i. the decrease of CD99 leads to major changes in the proteomic profile of EWS cells and EVs; ii. intracellular and extracellular compartments display two distinct signatures of differentially expressed proteins; iii. proteomic changes converge to the modulation of cell migration and immune-modulation biological processes; iv. CD99-silenced cells and related EVs are characterized by a migration-suppressive, pro-immunostimulatory proteomic profile. Overall, our data provide a novel source of CD99-associated protein biomarkers to be considered for further validation as mediators of EWS malignancy and as EWS disease liquid biopsy markers.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Extracellular Exosome

DISEASE(S): Peripheral Primitive Neuroectodermal Tumor

SUBMITTER: Marcello Manfredi

LAB HEAD: Marcello Manfredi

PROVIDER: PXD046846 | Pride | 2024-05-22

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	Esosomi_Bologna_CD99_23_1_Orbitrap_17122020_LIB1.mgf	Mgf
	Esosomi_Bologna_CD99_23_1_Orbitrap_17122020_LIB1.raw	Raw
	Esosomi_Bologna_CD99_23_1_Orbitrap_17122020_LIB2.mgf	Mgf
	Esosomi_Bologna_CD99_23_1_Orbitrap_17122020_LIB2.raw	Raw
	Esosomi_Bologna_CD99_23_2_Orbitrap_17122020_LIB1.mgf	Mgf

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Publications

CD99 Modulates the Proteomic Landscape of Ewing Sarcoma Cells and Related Extracellular Vesicles.

De Feo Alessandra A Manfredi Marcello M Mancarella Caterina C Maqueda Joaquín J JJ De Giorgis Veronica V Pignochino Ymera Y Sciandra Marika M Cristalli Camilla C Donadelli Massimo M Scotlandi Katia K

International journal of molecular sciences 20240127 3

Ewing sarcoma (EWS) is an aggressive pediatric bone tumor characterized by unmet clinical needs and an incompletely understood epigenetic heterogeneity. Here, we considered CD99, a major surface molecule hallmark of EWS malignancy. Fluctuations in CD99 expression strongly impair cell dissemination, differentiation, and death. CD99 is also loaded within extracellular vesicles (EVs), and the delivery of CD99-positive or CD99-negative EVs dynamically exerts oncogenic or oncosuppressive functions to ...[more]

PMID: 38338867

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Project description:Background: Acute coronary syndromes (ACS) are associated with aberrant gene expression and epigenetic mechanisms. In particular, de novo DNA methylation is typically linked to gene silencing, but its role in heart disease remains not fully understood. Extracellular vesicles (EVs) are active components in cellular communication for their ability to carry a plethora of signalling biomolecules, thus representing a promising new diagnostic/therapeutic approach in cardiovascular diseases (CVDs). Indeed, there is the need of novel biomarkers for ACS prediction and timely detection. Purpose: We hypothesized that specific epigenetic signals can be carried by EVs. In this regard, we isolated and characterized circulating EVs from ACS patients and evaluated their potential role to influence DNA methylation in target cells. Methods: Circulating EVs were recovered, by ultracentrifugation, from plasma samples of 19 ACS patients and 50 healthy subjects (HS). Nanoparticle tracking analysis (NTA) and western blot (WB) were used to confirm the EVs integrity and purity. Peripheral blood mononuclear cells (PBMCs) of volunteer donors were treated with both ACS and HS derived EVs and genomic DNA was extracted to perform epigenome wide analysis through Reduced Representation Bisulfite Sequencing. ShinyGO, PANTHER, and STRING tools were interrogated to perform GO and PPI network analyses. Flow Cytometry, qRT-PCR, and WB analysis were also performed to evaluate and validate both intra-vesicular and intra-cellular signals. Results: Plasma ACS-derived EVs showed a significant up-regulation of DNA methyltransferases (DNMTs) gene expression levels as compared to HS (P<0.001). Specifically, de novo methylation transcripts, as DNMT3A and DNMT3B were significantly increased in plasma ACS-EVs. DNA methylation analysis of PBMCs from volunteer donors treated with HS- and ACS-derived EVs showed that RNF166 and CCND3 genes resulted the most hyper- and hypo-methylated, respectively, after by ACS-EV treatment. In addition, PPI network analysis specifically evidenced the subnetwork with SRC, as a hub gene, connecting it to NOTCH1, FOXO3, CDC42, IKBKG, RXRA, DGKG, known as important genes already involved in the onset of CVDs. Surprising, other novel genes, BAIAP2, SYP, CHL1, and SHB, which were hypomethylated, were found significantly overexpressed in PBMCs (P<0.005), underlying the fundamental modulating properties of EV cargo in atherosclerosis. Conclusions: These findings support the significant role of ACS plasma-derived EVs, inducing de novo DNA methylation signals, and modulating specific signaling pathways in target cells.