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-1α (SDF-1α) 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 medi...

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Bibliographic Details
Published inBlood Vol. 97; no. 2; pp. 346 - 351
Main Authors Sanz-Rodrı́guez, Francisco, Hidalgo, Andrés, Teixidó, Joaquin
Format Journal Article
LanguageEnglish
Published Washington, DC Elsevier Inc 15.01.2001
The Americain Society of Hematology
Subjects
Biological and medical sciences
Immunodeficiencies. Immunoglobulinopathies
Immunoglobulinopathies
Immunopathology
Medical sciences
Human
Immunopathology
Vascular cell adhesion molecule 1
Migration
Cell microenvironment
Malignant hemopathy
Chemokine receptor
Myeloma
Adhesion
Fibronectin
Cell motility
Stromal cell derived factor 1
Integrin
Immunoglobulinopathy
Lymphoproliferative syndrome
Established cell line
Bone marrow
CXC chemokine
Tumor cell
Biological receptor
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Summary:The chemokine stromal cell-derived factor-1α (SDF-1α) 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 CD38hiCD45RA− BM cells and myeloma-derived cell lines expressed CXCR4 and displayed a moderate chemotactic response to SDF-1α. Because cell migration in response to SDF-1α might require a dynamic regulation of integrin function, it was investigated whether SDF-1α can modulate VLA-4 function on myeloma cells. SDF-1α 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 Gi protein downstream signaling and an intact cytoskeleton. Modulation of VLA-4–dependent myeloma cell adhesion by SDF-1α could contribute to the trafficking and localization of these cells in the BM microenvironment.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V97.2.346