PXD055337

PXD055337 is an original dataset announced via ProteomeXchange.

Title	CCR1 inhibition sensitizes multiple myeloma cells to glucocorticoid therapy
Description	One of the cornerstone drugs in the treatment of multiple myeloma (MM) are glucocorticoids. Because MM cells hijack the bone marrow microenvironment to obtain growth and survival signals, resistance to glucocorticoid-induced apoptosis emerges, yet, the underlying mechanisms remain poorly characterized. Here we identify that the chemokine receptor CCR1 together with its main ligand CCL3, plays a pivotal role in reducing glucocorticoid sensitivity of MM cells. We show that blocking of CCR1 signalling with the antagonist BX471 enhances the anti-MM effects of the glucorticoid dexamethasone in several MM cell lines, primary patient material and in a myeloma xenograft mouse model. Mechanistically, the drug combination shifts the balance between pro- and antiapoptotic proteins towards apoptosis and deregulates lysosomal proteins. We further find that the glucocorticoid-induced downregulation of CCR1 mRNA and protein is blunted in a glucocorticoid-resistance onset model. Finally, we demonstrate that CCR1 inhibition partially reverses GC-resistance, hereby offering a viable glucocorticoid resensitization strategy for MM treatment.
HostingRepository	PRIDE
AnnounceDate	2025-06-18
AnnouncementXML	Submission_2025-06-18_04:53:15.247.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sara Dufour
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 240

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-29 01:22:13	ID requested
⏵ 1	2025-06-18 04:53:16	announced

Luyckx B, Van Trimpont M, Declerck F, Staessens E, Verhee A, T'Sas S, Eyckerman S, Offner F, Van Vlierberghe P, Goossens S, Clarisse D, De Bosscher K, CCR1 inhibition sensitizes multiple myeloma cells to glucocorticoid therapy. Pharmacol Res, 215():107709(2025) [pubmed]

10.1016/j.phrs.2025.107709;

submitter keyword: Myeloma,Glucocorticoids, Dexamethasone, CCR1, BX471

Karolien De Bosscher1,2,3
contact affiliation	1VIB Center for Medical Biotechnology (CMB), Ghent, 2Belgium Department of Biomolecular Medicine, Ghent University, Ghent, Belgium, 3Cancer Research Institute Ghent (CRIG), Ghent, Belgium.
contact email	karolien.debosscher@vib-ugent.be
lab head
Sara Dufour
contact affiliation	VIB-UGent
contact email	sara.dufour@vib-ugent.be
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/2025/06/PXD055337

PRIDE project URI

• PRIDE
  1. PXD055337
     1. Label: PRIDE project
     2. Name: CCR1 inhibition sensitizes multiple myeloma cells to glucocorticoid therapy