VLA-4-dependent myeloma cell adhesion

In multiple myeloma, the malignant plasma cells in the bone marrow attach t o stromal elements using several adhesion receptors. The integrin VLA-4 pla ys a major role in mediating myeloma cell adhesion to the stroma, by intera cting with its ligands VCAM-1 and fibronectin. VLA-4, as well as other inte grins, can be expressed in different states of activation, which convey dif ferent levels of adhesion. Modulation of VLA-4 adhesive activity by externa l stimuli has been demonstrated for hematopoietic progenitor cells and lymp hocytes. and can represent a potential mechanism contributing to the locali zation of myeloma cells in the bone marrow, In this review we have summariz ed data on the characterization of VLA-4-mediated myeloma cell adhesion, an d we present potential mechanisms of modulation of VLA-4 activity. In addit ion, we also speculate on the signalling generated upon interaction of myel oma VLA-4 with its ligands on the survival of these cells in the bone marro w.