β3 integrin subunit mediates the bone-resorbing function exerted by cultured myeloma plasma cells

αvβ3 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 αvβ3 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 vβ3 transcriptional pathway in the bone-resorbing cells. Silencing of β3 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 β3-deficient cells from patients with no skeleton disease. Microarray gene analysis of β3+ myeloma cells showed that several osteoclast-related genes were up-regulated. Their functions include the activation of receptor pathways β3 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 β3 subunit of the integrin. ©2009 American Association for Cancer Research