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VLA-4-dependent myeloma cell adhesion
1Centro de Investigaciones Biológicas, Departamento de Inmunología Velázquez 144, 28006 Madrid, Spain.
In multiple myeloma, the malignant plasma cells in the bone marrow attach to stromal elements using several adhesion receptors. The integrin VLA-4 plays a major role in mediating myeloma cell adhesion to the stroma, by interacting with its ligands VCAM-1 and fibronectin. VLA-4, as well as other integrins, can be expressed in different states of activation, which convey different levels of adhesion. Modulation of VLA-4 adhesive activity by external stimuli has been demonstrated for hematopoietic progenitor cells and lymphocytes, and can represent a potential mechanism contributing to the localization of myeloma cells in the bone marrow. In this review we have summarized data on the characterization of VLA-4-mediated myeloma cell adhesion, and we present potential mechanisms of modulation of VLA-4 activity. In addition, we also speculate on the signalling generated upon interaction of myeloma VLA-4 with its ligands on the survival of these cells in the bone marrow.
In multiple myeloma, the malignant plasma cells in the bone marrow attach to stromal elements using several adhesion receptors. The integrin VLA-4 plays a major role in mediating myeloma cell adhesion to the stroma, by interacting with its ligands VCAM-1 and fibronectin. VLA-4, as well as other integrins, can be expressed in different states of activation, which convey different levels of adhesion. Modulation of VLA-4 adhesive activity by external stimuli has been demonstrated for hematopoietic progenitor cells and lymphocytes, and can represent a potential mechanism contributing to the localization of myeloma cells in the bone marrow. In this review we have summarized data on the characterization of VLA-4-mediated myeloma cell adhesion, and we present potential mechanisms of modulation of VLA-4 activity. In addition, we also speculate on the signalling generated upon interaction of myeloma VLA-4 with its ligands on the survival of these cells in the bone marrow.