Dataset Information

Targeting of CD30-negative tumor cells in DLBCL with Brentuximab-vedotin through CD30-positive extracellular vesicles, in vitro

ABSTRACT: Evaluate the composition of extracellular vesicles by mass spectrometry coupled with liquid chromatography.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, Cell Suspension Culture

DISEASE(S): Hodgkin's Lymphoma

SUBMITTER: Adriana Franco Paes Leme

LAB HEAD: Adriana Franco Paes Leme

PROVIDER: PXD025442 | Pride | 2022-02-17

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	09marc_Hinrich_C1011_2.msf	Msf
	09marc_Hinrich_C1011_2.raw	Raw
	09marc_Hinrich_C1011_3.msf	Msf
	09marc_Hinrich_C1011_3.raw	Raw
	09marc_Hinrich_C1011_4.msf	Msf

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Publications

CD30-Positive Extracellular Vesicles Enable the Targeting of CD30-Negative DLBCL Cells by the CD30 Antibody-Drug Conjugate Brentuximab Vedotin.

Lobastova Liudmila L Lettau Marcus M Babatz Felix F de Oliveira Thais Dolzany TD Nguyen Phuong-Hien PH Pauletti Bianca Alves BA Schauss Astrid C AC Dürkop Horst H Janssen Ottmar O Paes Leme Adriana F AF Hallek Michael M Hansen Hinrich P HP

Frontiers in cell and developmental biology 20210730

CD30, a member of the TNF receptor superfamily, is selectively expressed on a subset of activated lymphocytes and on malignant cells of certain lymphomas, such as classical Hodgkin Lymphoma (cHL), where it activates critical bystander cells in the tumor microenvironment. Therefore, it is not surprising that the CD30 antibody-drug conjugate Brentuximab Vedotin (BV) represents a powerful, FDA-approved treatment option for CD30<sup>+</sup> hematological malignancies. However, BV also exerts a stron ...[more]

PMID: 34395429

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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.