Open AccessMobilization of Myeloma Cells Involves SDF‐1/CXCR4 Signaling and Downregulation of VLA‐4
Author(s) -
Gazitt Yair,
Akay Cagla
Publication year - 2004
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.22-1-65
Subject(s) - biology , downregulation and upregulation , multiple myeloma , cxcr4 , mobilization , cancer research , microbiology and biotechnology , signal transduction , immunology , genetics , gene , chemokine , history , immune system , archaeology
Adhesion molecules and stromal cell‐derived factor‐1 (SDF‐1)/CXCR4 signaling play key roles in homing and mobilization of hematopoietic stem cells (HSC). Active signaling through SDF‐1/CXCR4 and upregulation of adhesion molecules are required for homing, whereas downregulation of adhesion molecules and disruption of SDF‐1/CXCR4 signaling are required for mobilization of HSC. We studied the surface expression of CXCR4 very late activation antigen (VLA)‐4 and VLA‐5 on myeloma cells mobilized with cyclophosphamide and GM‐CSF in 12 multiple myeloma patients undergoing HSC mobilization for autologous transplantation. We also studied the plasma levels of SDF‐1 in apheresis collection of these patients. We observed a statistically significant decrease in the levels of SDF‐1 and surface expression of CXCR4 on myeloma cells in four consecutive apheresis collections compared with premobilization bone marrow specimens. We also observed a statistically significant decrease in surface expression of VLA‐4 in myeloma cells in the apheresis collections compared with premobilization bone marrow samples. Furthermore, myeloma cells derived from apheresis collections had decreased adhesion and trans‐stromal migration in response to SDF‐1, which could be reversed by short incubation with interleukin‐6. Hence, mobilization of myeloma cells involves SDF‐1/CXCR4 signaling and downregulation of VLA‐4.