Chemokine stromal cell-derived factor-1alpha modulates VLA-4 integrin-mediated multiple myeloma cell adhesion to CS-1/fibronectin and VCAM-1.
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.
Sanz-Rodríguez
F
F
Department of Immunology, Centro de Investigaciones Biológicas, Madrid, Spain.
Hidalgo
A
A
Teixidó
J
J
D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002469:Cell Separation; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology* / Q000502:physiology; D002633:Chemotaxis / Q000187:drug effects; D015638:Cytochalasin D / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000187:drug effects* / Q000502:physiology; D007700:Kinetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009101:Multiple Myeloma / Q000473:pathology* / Q000503:physiopathology; D009194:Myeloma Proteins / Q000378:metabolism / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D009842:Oligopeptides / Q000378:metabolism*; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000187:drug effects* / Q000502:physiology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism* / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
C515255:CXCL12 protein, human; D002352:Carrier Proteins; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D009194:Myeloma Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D009842:Oligopeptides; D019718:Receptors, CXCR4; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D010566:Virulence Factors, Bordetella; C094697:glutamyl-isoleucyl-leucyl-aspartyl-valine; D015638:Cytochalasin D; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases; D019950:Mitogen-Activated Protein Kinase 1