Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Bone Marrow Cells / metabolism
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Bone Marrow Cells / pathology
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Carrier Proteins / metabolism*
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Cell Adhesion / drug effects
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Cell Separation
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Chemokine CXCL12
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Chemokines, CXC / pharmacology*
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Chemokines, CXC / physiology
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Chemotaxis / drug effects
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Cytochalasin D / pharmacology
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Fibronectins / metabolism*
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Humans
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Integrin alpha4beta1
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Integrins / drug effects*
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Integrins / physiology
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Kinetics
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Mitogen-Activated Protein Kinase 1 / metabolism
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Multiple Myeloma / pathology*
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Multiple Myeloma / physiopathology
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Myeloma Proteins / metabolism
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Myeloma Proteins / pharmacology
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Nucleic Acid Synthesis Inhibitors / pharmacology
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Oligopeptides / metabolism*
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Pertussis Toxin
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Phosphatidylinositol 3-Kinases / metabolism
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Receptors, CXCR4 / metabolism
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Receptors, Lymphocyte Homing / drug effects*
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Receptors, Lymphocyte Homing / physiology
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Tumor Cells, Cultured
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Up-Regulation / drug effects
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Vascular Cell Adhesion Molecule-1 / metabolism*
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Vascular Cell Adhesion Molecule-1 / physiology
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Virulence Factors, Bordetella / pharmacology
Substances
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CXCL12 protein, human
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Carrier Proteins
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Chemokine CXCL12
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Chemokines, CXC
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Fibronectins
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Integrin alpha4beta1
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Integrins
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Myeloma Proteins
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Nucleic Acid Synthesis Inhibitors
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Oligopeptides
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Receptors, CXCR4
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Receptors, Lymphocyte Homing
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Vascular Cell Adhesion Molecule-1
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Virulence Factors, Bordetella
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glutamyl-isoleucyl-leucyl-aspartyl-valine
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Cytochalasin D
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Pertussis Toxin
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Phosphatidylinositol 3-Kinases
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Mitogen-Activated Protein Kinase 1