Stromal-derived factor 1 and matrix metalloproteinase 9 levels in bone marrow and peripheral blood of patients mobilized by granulocyte colony-stimulating factor and chemotherapy. Relationship with mobilizing capacity of haematopoietic progenitor cells.
The roles of the chemokine stromal-derived factor 1 (SDF-1) and the matrix metalloproteinase 9 (MMP-9) in haematopoietic progenitor cell (HPC) mobilization are still unclear, particularly when patients are mobilized by granulocyte colony-stimulating factor (G-CSF) plus chemotherapy. We determined bone marrow (BM) and peripheral blood (PB) plasma levels of SDF-1, together with CXC-chemokine receptor 4 (CXCR-4) expression on CD34+ cells, and interleukin 8 (IL-8) and MMP-9 in 55 patients mobilized for autologous PB transplantation compared with 10 normal BM and PB samples. Plasma samples were tested at steady state (SS-) and after mobilization by cyclophosphamide and G-CSF administration (M-). SDF-1, CXCR-4, IL-8 and MMP-9 levels were significantly lower in SS- and M-PB than in SS-BM. Differences in SDF-1 levels between SS-PB and SS-BM were also observed after mobilization. We showed for the first time a clear relationship between the levels of circulating HPC, both at steady state and after mobilization, and those of secreted MMP-9 but not of SDF-1 or IL-8. However, a negative correlation was observed between mobilizing capacity and CXCR-4 expression on CD34+ cells. These findings suggest that G-CSF-induced mobilization of HPC from BM involves MMP-9, without reversing the positive gradient of SDF-1 between BM and PB.
Carion
Alexandra
A
Laboratory of Haematology, Department of Medical Oncology, and Regional Blood Bank, UPRES-EA3249, Faculty of Medicine and University Hospital of Tours, Tours, France.
Benboubker
Lotfi
L
Hérault
Olivier
O
Roingeard
Françoise
F
Degenne
Michel
M
Senecal
Delphine
D
Desbois
Isabelle
I
Colombat
Philippe
P
Charbord
Pierre
P
Binet
Christian
C
Domenech
Jorge
J
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D000970:Antineoplastic Agents / Q000494:pharmacology; D001853:Bone Marrow / Q000378:metabolism; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000097:blood / Q000378:metabolism*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D019718:Receptors, CXCR4 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D018952:Antigens, CD34; D000970:Antineoplastic Agents; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D016209:Interleukin-8; D019718:Receptors, CXCR4; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D020780:Matrix Metalloproteinase 9