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Blood, 15 January 2001, Vol. 97, No. 2, pp. 346-351
CHEMOKINES
Chemokine stromal cell-derived factor-1 modulates VLA-4
integrin-mediated multiple myeloma cell adhesion to CS-1/fibronectin
and VCAM-1
Francisco Sanz-Rodríguez,
Andrés Hidalgo, and
Joaquin Teixidó
From the Department of Immunology, Centro de
Investigaciones Biológicas, Madrid, Spain.
The chemokine stromal cell-derived factor-1 (SDF-1) 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-1. Because cell migration in response to SDF-1
might require a dynamic regulation of integrin function, it was
investigated whether SDF-1 can modulate VLA-4 function on myeloma
cells. SDF-1 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-1 could contribute to the trafficking and localization of these cells in the BM microenvironment.
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