Expression of macrophage inhibitory cytokine-1 in prostate cancer bone metastases induces osteoclast activation and weight loss.

摘要: BACKGROUND Macrophage inhibitory cytokine-1 (MIC-1) belongs to the bone morphogenic protein/transforming growth factor-β (BMP/TGF-β) superfamily. Serum MIC-1 concentrations are elevated in patients with advanced prostate cancer. The effects of on cancer metastases unknown. METHODS In vitro osteoblast differentiation and activity were analyzed alkaline phosphatase mineralization assays; osteoclast numbers counted microscopically. TLR9 expression studied Western blotting. Human Du-145 cells stably transfected a cDNA encoding for mature or an empty vector. vivo characteristics characterized intra-tibial model metastasis. Tumor associated changes viewed X-rays, histology, histomorphometry. Bone formation was assayed by measuring serum PINP. RESULTS MIC-1 induced vitro. These independent expression, which promoted MIC-1. Both control tumors mixed sclerotic/lytic lesions, but increased osteolytic component tumors. Osteoclast at tumor–bone interface significantly higher tumors, whereas mice. At sacrifice, mice bearing lighter smaller tumors. CONCLUSIONS MIC-1 up-regulates various cells. stimulates both vitro, independently TLR9. over-expressing that grow induce cachexia. Prostate 69:652–661, 2009. © 2009 Wiley-Liss, Inc.