Interleukin-6 receptor inhibitor suppresses bone metastases in a breast cancer cell line.

BACKGROUND: Interleukin-6 (IL-6) is a potent inflammatory cytokine that appears to play a key role in cancer growth and metastasis. In the present study, the effects of IL-6 receptor (IL-6R) on breast cancer aggressiveness and bone metastases were investigated. METHODS: MDA-MB-231 (MDA-231) cells were treated in the presence or absence of anti-human IL-6 receptor (IL-6R) monoclonal antibody and examined with respect to cell survival. The expressions of signal transducer and activator of transcription 3 (Stat3), vascular endothelial growth factor (VEGF), and receptor activator of NF-κB (RANK) were analyzed by SDS-PAGE and immunoblotting. MDA-231 cells were injected into the left ventricle of mice, and then anti-human IL-6R monoclonal antibody or saline was administered intraperitoneally for 28 days. After 28 days, the incidence of bone metastases was evaluated in the hind limbs by radiography and histology. RESULTS: Anti-human IL-6R monoclonal antibody reduced bone metastases in an animal model injected with MDA-231 cells on radiological and histomorphometric analyses. The mechanism of bone metastasis inhibition involved inhibited cell proliferation and decreased expressions of phospho-Stat3, VEGF, and RANK in MDA-231 cells. CONCLUSIONS: The results of the present study suggest that inhibition of IL-6 signaling may become a preventive therapeutic option for breast cancer and bone metastases.

Prosthetic limb salvage surgery for bone and soft tissue tumors around the knee.

In this study, we analyzed long-term survival, limb function and associated complications after prosthetic limb salvage treatment in patients with bone and soft tissue tumors around the knee joint. A total of 63 patients treated with prosthetic limb salvage surgery around the knee were reviewed. The bone tumors involved the distal femur in 45 patients, the proximal tibia in 14 patients and the soft tissue tumors of the proximal lower leg in 4 patients. The median follow-up period after the first operation was 8.0 years. The medical records of the patients, surgical reports, radiographs and histological specimens were retrospectively reviewed. The 5-year overall survival rate was 63.2% in the patients with distal femur tumors and 86.2% in those with tumors of the proximal lower leg. The 5­year prosthetic survival rate was 72.8% in the distal femur and 74.6% in the proximal lower leg. The mean functional score according to the scoring system of the Musculoskeletal Tumor Society (MSTS) was 81% in the patients with distal femur tumors and 82% in the patients with proximal lower leg tumors. Post-operative complications occurred in 27 patients. Limb salvage surgery is considered to be an effective treatment option. However, the high complication rate is a major concern for prosthetic replacement. Future improvements of prostheses are very important.

TNF inhibitor suppresses bone metastasis in a breast cancer cell line.

In the evolution of cancer, tumor necrosis factor-alpha (TNF-α) plays a paradoxical role. High doses induce significant anticancer effects, but conversely, physiologic and pathologic levels of TNF-α may be involved in cancer promotion, tumor growth, and metastasis. Infliximab is a chimeric murine monoclonal antibody that binds with high affinity to soluble and membrane TNF-α and inhibits binding of TNF-α to its receptors. In the present study, we investigated the effect of infliximab, a TNF-α antagonist, on breast cancer aggressiveness and bone metastases. Infliximab greatly reduced cell motility and bone metastases in a metastatic breast cancer cell line, MDA-MB-231. The mechanism of bone metastasis inhibition involved decreased expression of CXC chemokine receptor 4 (CXCR4) and increased expression of decorin, which is the prototype of an expanding family of small leucine-rich proteoglycans. These results suggest a novel role for TNF-α inhibition in the reduction or prevention of bone metastases in this breast cancer model. Our study suggests that inhibition of TNF-α using infliximab may become a preventive therapeutic option for breast cancer.