Identification of breast cancer cell line-derived paracrine factors that stimulate osteoclast activity.

摘要: Metastatic breast cancer causes destruction of significant amounts bone, and, although bone is the most likely site metastasis, little understood about interactions between tumor cells and bone-resorbing osteoclasts. We have investigated paracrine factors produced by that are involved in increasing osteoclast activity. determined immunoassay human cell line MDA MB 231 (231) cultured serum-free medium secretes transforming growth type β (TGF-β) 1 2, macrophage colony-stimulating factor (M-CSF), granulocyte (GM-CSF), interleukin (IL) -1 -6, necrosis α (TNF-α), insulin-like II (IGF II), parathyroid hormone-related peptide. To determine which these increased destruction, we fractionated 231-conditioned media measured fractions for effects on resorption activity using multiple assays. The pattern responses was complex. Several stimulated either number osteoclasts binding to or elevating individual Other inhibited Analysis active identified revealed presence TNF-α IGF-II restricted separate contained M-CSF, IL-6, TGF-β2, GM-CSF. No TGF-β1 IL-1 detected any fractions. Our data support hypothesis modulate regulatory increase both mature attached Once it how metastatic elevates osteoclast-mediated loss, effective therapies slow progression and/or prevent this loss will become possible.