Bone Abstracts

Background: We have recently identified interleukin 1B (IL-1B) as a potential biomarker for predicting breast cancer patients at increased risk for developing bone metastasis. In mouse models, IL-1B and its receptor (IL-1R1) are upregulated in breast cancer cells that metastasise to bone compared with cells that do not. We have now investigated whether blocking IL-1R with the clinically licensed antagonist, anakinra, might be a potential treatment for breast cancer and bone metastasis.

Methodology: In vitro analysis of proliferation, migration and invasion were carried out in MDA-MB-231-IV, MCF7 and T47D cells treated with anakinra and/or IL-1B. For in vivo experiments mice received a subcutaneous implantation of MDA-MB-IV, MCF7 or T47D cells or intra-venous injection of MDA-MB-231-IV cells. Anakinra (1 mg/kg per day) or placebo was administered 3-days before (preventative) or 7-days later (treatment). Tumour volume was measured using callipers, apoptosis (TUNEL, Caspase 3), proliferation (Ki67) and angiogenesis (CD34, immunohistochemistry, VEGF and endothelin (qPCR)). Effects on bone were measured by uCT, and TRAP, P1NP, IL-1B, TNF alpha and IL-6 ELISA.

Results: Anakinra significantly reduced growth of MDA-MB-231-IV tumours in bone from 6.50±3.00 mm² (placebo) to 2.56±1.07 mm² (treatment) and 0.63±0.18 mm² (preventative). Anakinra also reduced the number of mice that developed bone metastasis from 90% (placebo) to 40% (treatment) and 10% (preventative). Anti-tumour effects were not confined to bone, subcutaneous tumour volumes reduced from 656.68 mm³ (placebo) to 160.47 mm³ (treatment) and 31.08 mm³ (preventative). Anakinra did not increase tumour cell apoptosis but reduced proliferation and angiogenesis in addition to exerting significant effects on the tumour environment reducing bone turnover markers, IL-1B and TNF alpha. Anakinra had no effect on proliferation, migration or invasion of breast cancer cells in vitro.

Conclusions: Anakinra inhibits breast cancer growth and bone metastases in vivo by altering the tumour microenvironment.