cytochalasin-d and Multiple-Myeloma

The chemokine stromal cell-derived factor-1alpha (SDF-1alpha) 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-1alpha. Because cell migration in response to SDF-1alpha might require a dynamic regulation of integrin function, it was investigated whether SDF-1alpha can modulate VLA-4 function on myeloma cells. SDF-1alpha 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(i) protein downstream signaling and an intact cytoskeleton. Modulation of VLA-4-dependent myeloma cell adhesion by SDF-1alpha could contribute to the trafficking and localization of these cells in the BM microenvironment.

Topics: Bone Marrow Cells; Carrier Proteins; Cell Adhesion; Cell Separation; Chemokine CXCL12; Chemokines, CXC; Chemotaxis; Cytochalasin D; Fibronectins; Humans; Integrin alpha4beta1; Integrins; Kinetics; Mitogen-Activated Protein Kinase 1; Multiple Myeloma; Myeloma Proteins; Nucleic Acid Synthesis Inhibitors; Oligopeptides; Pertussis Toxin; Phosphatidylinositol 3-Kinases; Receptors, CXCR4; Receptors, Lymphocyte Homing; Tumor Cells, Cultured; Up-Regulation; Vascular Cell Adhesion Molecule-1; Virulence Factors, Bordetella