Chemokine stromal cell-derived factor-1α modulates VLA-4 integrin-mediated multiple myeloma cell adhesion to CS-1/fibronectin and VCAM-1

The chemokine stromal cell-derived factor-1 alpha (SDF-1 alpha) and its G-protein-linked receptor CXCR4 are involved in hematopoietic progenitor cell and lymphocyte migration. The integrin VLA-4 is a cell adhesion receptor for CS-1/fibronectin and VCAM-1 and constitutes one of the main adhesion receptors mediating myeloma cell adhesion to bone marrow (BM) stroma in multiple myeloma (MM), It is shown here that MM CD38(hi)CD45RA(-) BM cells and myeloma-derived cell lines expressed CXCR4 and displayed a moderate chemotactic response to SDF-1 alpha. Because cell migration in response to SDF-1 alpha might require a dynamic regulation of integrin function, it was investigated whether SDF-1 alpha can modulate VLA-4 function on myeloma cells. SDF-1 alpha rapidly and transiently up-regulated VLA-4-mediated myeloma cell adhesion to both CS-1/fibronectin and VCAM-1,which was inhibited by pertussis toxin and cytochalasin D, indicating the involvement of G(1) protein downstream signaling and an intact cytoskeleton, Modulation of VLA-4-dependent myeloma cell adhesion by SDF-1 alpha could contribute to the trafficking and localization of these cells in the BM microenvironment. (C) 2001 by The American Society of Hematology.