Multiple myeloma plasma cells show different chemokine receptor profiles at sites of disease activity.
Chemokines and their receptors play a pivotal role in the regulation of B-lymphocyte trafficking. This study was aimed at investigating the pattern of chemokine receptor expression, including CCR1 to CCR3, CCR5 to CCR7, CXCR1 to CXCR5, and the migration ability of multiple myeloma (MM) plasma cells (PC). PC were recovered from the bone marrow (BM) of 29 MM patients, extramedullary sites of 10 patients and the BM of five controls. Flow cytometry analysis showed that the receptors mainly expressed on malignant BM PC were represented by CXCR4 (70% of patients), CCR1 (25%), CCR2 (25%), CCR5 (17%) and CXCR3 (20%), while other receptors were commonly lacking. The analysis performed on extramedullary (peripheral blood and pleural effusion) malignant PC demonstrated that the most represented receptors were CXCR4 (100%), CCR2 (66%) and CXCR1 (60%). The migratory capability of malignant PC at resting conditions identified three groups of patients with different migration (low, intermediate and high). As CXCR4 was the relevant chemokine receptor expressed by MM PC, its ligand CXCL12 induced their migration. These data suggest that malignant PC from MM display different chemokine receptor profiles and that CXCR4 is fully functional and might play a role in the spreading of the disease.
Trentin
Livio
L
Department of Clinical and Experimental Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, Padua, Italy.
Miorin
Marta
M
Facco
Monica
M
Baesso
Ilenia
I
Carraro
Samuela
S
Cabrelle
Anna
A
Maschio
Nilla
N
Bortoli
Michela
M
Binotto
Gianni
G
Piazza
Francesco
F
Adami
Fausto
F
Zambello
Renato
R
Agostini
Carlo
C
Semenzato
Gianpietro
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000276:immunology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology*; D010950:Plasma Cells / Q000276:immunology*; D010996:Pleural Effusion / Q000276:immunology; D054390:Receptors, CCR2; D019718:Receptors, CXCR4 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism*; D023062:Receptors, Interleukin-8A / Q000378:metabolism; D014407:Tumor Cells, Cultured
C515334:CCR2 protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D054390:Receptors, CCR2; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D023062:Receptors, Interleukin-8A