PXD069251

PXD069251 is an original dataset announced via ProteomeXchange.

Title	Small extracellular vesicles secreted by cisplatin-resistant neuroblastoma cells increase lactate secretion and alter metabolic pathways in primary human umbilical vein endothelial cells (HUVECs)
Description	Background: Chemoresistance, particularly to cisplatin, remains a significant challenge in treating high-risk neuroblastoma, resulting in a mere 20% five-year overall survival rate. Tumour-derived small extracellular vesicles (sEVs) have been implicated in cancer progression by promoting angiogenesis, invasion, and proliferation in recipient cells. This study investigated alterations in the protein cargo of sEVs secreted by cisplatin-sensitive and resistant neuroblastoma cells and their impact on reprogramming non-cancerous recipient cells. Methods: sEVs from cisplatin-resistant (KellyCis83) and its cisplatin-sensitive parental cell line (Kelly) were isolated and characterised, followed by proteomic profiling and Gene Set Enrichment Analysis. Functional assays using human umbilical vein endothelial cells (HUVECs) evaluated the effects of sEVs on proliferation, migration, tube formation, and metabolism. The clinical relevance of the shortlisted sEV glycolytic proteins were evaluated using the R2 Genomics Analysis and Visualisation Platform. Results: Proteomic analysis revealed dysregulated metabolic pathways in KellyCis83 sEVs. While the Kelly’s and KellyCis83’s sEV-induced aerobic glycolytic rate was similar, oxidative phosphorylation (OXPHOS) was significantly reduced in HUVECs treated with Kelly’s sEVs compared to KellyCis83’s sEVs, which may be due to an altered balance of glycolytic enzymes in sEVs. Under angiogenic factor-deprived conditions, the uptake of sEVs by HUVECs reduced their proliferation and increased anchorage-dependent differentiation. Our study demonstrated the enrichment of the MYCN oncogene and clinically relevant glycolytic proteins in neuroblastoma cell-derived sEVs. Conclusion: This study reports a potential mechanism by which sEVs derived from cisplatin-resistant neuroblastoma cells modulate endothelial cell function through alterations in metabolic pathways and provides an opportunity to explore exosomal MYCN and glycolytic proteins as circulating biomarkers for progression and treatment response signatures, using less invasive methods and enabling personalised treatment approaches for neuroblastoma patients.
HostingRepository	PRIDE
AnnounceDate	2025-11-04
AnnouncementXML	Submission_2025-11-04_05:02:35.555.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eugene Dillon
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-09 05:44:23	ID requested
⏵ 1	2025-11-04 05:02:36	announced

Dataset with its publication pending

submitter keyword: extracellular vesicles

Vadim Zhernovkov
contact affiliation	Systems Biology Ireland, School of Medicine, University College Dublin, Ireland
contact email	vadim.zhernovkov@ucd.ie
lab head
Eugene Dillon
contact affiliation	UCD
contact email	eugene.dillon@ucd.ie
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD069251
     1. Label: PRIDE project
     2. Name: Small extracellular vesicles secreted by cisplatin-resistant neuroblastoma cells increase lactate secretion and alter metabolic pathways in primary human umbilical vein endothelial cells (HUVECs)