PXD047285

PXD047285 is an original dataset announced via ProteomeXchange.

Title	Multiple myeloma derived extracellular vesicle uptake by monocyte cells stimulates secretion of IL-6 and MMP9 and promotes cancer cell migration and proliferation.
Description	Multiple Myeloma (MM) is an incurable haematological malignancy caused by uncontrolled growth of plasma cells. MM pathogenesis is largely attributed to crosstalk between plasma cells and the bone marrow microenvironment (BMM), where extracellular vesicles (EVs) are reported to play a role. Improved knowledge of the signals mediated by EVs is important to understand MM progression. In this study, EVs secreted from a panel of MM cell lines were isolated by ultracentrifugation. Fluorescently stained EVs were cultured with THP1 monocyte cells and EV uptake by monocytes was determined by flow cytometry and confocal microscopy. MM EVs from three cell lines displayed a differential yet dose dependent uptake by THP1 cells, with H929 EVs displaying greatest EV uptake compared to MM1.s and U266 EVs suggesting that uptake efficiency is dependent on the cell line of origin. Furthermore, MM EVs increased the secretion of MMP9 and IL6 from monocytes, with H929 EVs inducing greater effect, which is consistent with greater uptake efficiency. Moreover, monocyte conditioned media collected following H929 EV uptake significantly increased the migration and proliferation of MM cells indicating that MM EVs can modify the BMM towards a pro-tumourigenic and metastatic phenotype. Finally, mass spectrometry revealed different protein cargo within the MM EVs. Proteomic comparison between the MM-EVs indicated a correlation with proteins involved in exocytic secretion (RAB8b, Exoc4), splicing (FUS, SRPK2) and focal adhesion (integrins ITGB1, ITGA4) that are associated with disease progression. KEGG pathway analysis demonstrated a significant enrichment of spliceosome related proteins in H929 EVs compared to the U266 and MM1s EVs, which may contribute towards the altered BMM. Overall, our results indicate that MM derived EVs modulate monocyte function to promote tumour growth and metastasis.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:56:31.816.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kieran Wynne
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-27 09:57:03	ID requested
1	2024-08-26 06:29:04	announced
⏵ 2	2024-10-22 06:56:32	announced	2024-10-22: Updated project metadata.

10.3390/cancers16051011;

Sheridan R, Brennan K, Bazou D, O'Gorman P, Matallanas D, Mc Gee MM, Multiple Myeloma Derived Extracellular Vesicle Uptake by Monocyte Cells Stimulates IL-6 and MMP-9 Secretion and Promotes Cancer Cell Migration and Proliferation. Cancers (Basel), 16(5):(2024) [pubmed]

submitter keyword: Multiple myeloma, extracellular vesicle, cancer cell migration.

Prof Margaret McGee
contact affiliation	University College Dublin, School of Biomolecular and Biomedical Science, Conway Institute Belfield Dublin 4
contact email	margaret.mcgee@ucd.ie
lab head
Kieran Wynne
contact affiliation	University College Dublin
contact email	kieran.wynne1@ucd.ie
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/08/PXD047285

PRIDE project URI

• PRIDE
  1. PXD047285
     1. Label: PRIDE project
     2. Name: Multiple myeloma derived extracellular vesicle uptake by monocyte cells stimulates secretion of IL-6 and MMP9 and promotes cancer cell migration and proliferation.