Matrix metalloproteinases in multiple myeloma

Multiple myeloma is a deadly malignancy characterized by plasma cell infilt ration of bones. The resulting effect is painful "punched-out" lesions wher e bone is eroded and filled with myeloma cells that suppress and replace th e normal marrow components. Recently it has been shown that myeloma cells p roduce matrix-metalloproteinase-9 (MIMP-9) and MMP-2 and that accumulation of MMP-9 protein is suppressed upon expression of the heparan sulfate prote oglycan, syndecan-1. In this review, we briefly consider the potential role s for MMPs in the pathogenesis of multiple myeloma. MMPs likely have major roles in: 1) the infiltration of bone and other tissues by the myeloma cell s; 2) the osteolytic bone destruction caused by overly active osteoclasts, 3) extracellular matrix remodeling by bone marrow stromal cells; 4) promoti ng the invasion of the endothelial cells that form neoangiogenic blood vess els necessary to sustain tumor foci; and 5) promoting the growth of myeloma cells. Effective and safe synthetic inhibitors of MMPs are available and t hese may prove useful in limiting the growth and spread of myeloma cells. I n addition, recent insights into the suppression of MMP-9 by syndecan-1 may suggest new strategies for treatment of myeloma.