β3 Integrin Subunit Mediates the Bone-Resorbing Function Exerted by Cultured Myeloma Plasma Cells

α v β 3 integrin was investigated in multiple myeloma in relation to the in vitro osteoclast-like activity of malignant plasma cells. Myeloma cells from patients with skeleton involvement overexpressed α v β 3 and produced erosion pits on bone substrates, whereas this effect was not observed by cells from patients with no evidence of bone disease. We therefore explored the α v β 3 transcriptional pathway in the bone-resorbing cells. Silencing of β 3 chain abrogated the ability to produce erosion pits and extracellular signal-regulated kinase 1/2 phosphorylation resulting in the defective function of cFos and nuclear factor activator T cell 1, the terminal effectors of osteoclast activation. A similar defect occurred in constitutively β 3 -deficient cells from patients with no skeleton disease. Microarray gene analysis of β 3 + myeloma cells showed that several osteoclast-related genes were up-regulated. Their functions include the activation of receptor pathways β 3 and c-fms that regulate several osteoclast functions. These data emphasize the postulated role of myeloma cells in multiple myeloma bone disease and suggest that their osteoclast-like activity is regulated, at least in vitro , by the β 3 subunit of the integrin. [Cancer Res 2009;69(16):6738–46]