Dataset Information

CCR1 inhibition sensitizes multiple myeloma cells to glucocorticoid therapy

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Exploris 240

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Sara Dufour

LAB HEAD: Karolien De Bosscher1,2,3

PROVIDER: PXD055337 | Pride | 2025-06-18

REPOSITORIES: Pride

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			Action	DRS
	CMB-1460DIA_UPRC_9606_X00709_1p_Ionopticks3_PM2_CMB-1460_KADEB_1.raw	Raw
	CMB-1460DIA_UPRC_9606_X00711_1p_Ionopticks3_PM2_CMB-1460_KADEB_2.raw	Raw
	CMB-1460DIA_UPRC_9606_X00713_1p_Ionopticks3_PM2_CMB-1460_KADEB_3.raw	Raw
	CMB-1460DIA_UPRC_9606_X00715_1p_Ionopticks3_PM2_CMB-1460_KADEB_4.raw	Raw
	CMB-1460DIA_UPRC_9606_X00717_1p_Ionopticks3_PM2_CMB-1460_KADEB_5.raw	Raw

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CCR1 inhibition sensitizes multiple myeloma cells to glucocorticoid therapy.

Luyckx Bert B Van Trimpont Maaike M Declerck Fien F Staessens Eleni E Verhee Annick A T'Sas Sara S Eyckerman Sven S Offner Fritz F Van Vlierberghe Pieter P Goossens Steven S Clarisse Dorien D De Bosscher Karolien K

Pharmacological research 20250323

Glucocorticoids (GC) are cornerstone drugs in the treatment of multiple myeloma (MM). Because MM cells exploit 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 the glucocorticoid sensitivity of MM cells. We show that blocking CCR1 signaling ...[more]

PMID: 40132675

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