Bevacizumab: modulation of the bone microenvironment to reduce angiogenesis and metastasis?

37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, PCC174

Poster Communications: Bevacizumab: modulation of the bone microenvironment to reduce angiogenesis and metastasis?

S. Lunj1, M. W. Reed1, K. J. Reeves1, C. A. Staton1, I. Holen1, N. J. Brown1

1. Oncology, University of Sheffield, Sheffield, United Kingdom.

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Introduction: Bone metastasis is a major cause of breast cancer associated morbidity. Currently bisphosphonates are used to treat bone metastasis however no effective preventative measures are available. Vascular Endothelial Growth Factor A (VEGF) and associated receptor expression has been identified in bones from patients with metastatic breast cancer, representing a potential therapeutic target. Bevacizumab (Bz) inhibits VEGF-receptor interactions so may be effective in inhibiting angiogenesis and hence the formation of bone metastasis. Methodology: 6-week old Balb/c nude female mice were injected intra-cardiac in the left ventricle with 1×105 MDA-MB-231 luciferase labelled breast cancer cells under anaesthesia (isoflurane). Once bioluminescence (IVIS-Lumina2) was detected in bone by in vivo imaging, treatment commenced with Bz (0.1 or 0.5mg/kg, intraperitoneal twice-weekly for 6 weeks) or control vehicle (n=6/group). Tumour growth was monitored by twice weekly bioluminescence imaging. At the end of the experiment, hind limbs were harvested and processed for µCT analysis and bone histomorphometry. Results: Bz (0.1mg/kg) inhibits breast cancer-induced bone metastasis compared to the vehicle control (treatment vs. control; 1000000 vs. 790000 total flux [p/s]) however bone mineral density remains unchanged. Initial analysis of osteoblasts (Ob) and osteoclasts (Oc) not in direct contact with the tumour suggests there is no difference in Oc number present on the trabecular surfaces in Bz-treated or control animals (Osteoclasts: Bz vs control; 0.125 vs. 0 per mm trabecular bone surface). In contrast, there appears to be decreased Ob numbers in similar regions in the Bz treated group (Osteoblasts: Bz vs control; 2.6 Bz vs. 7.5 control). Conclusions: Preliminary data from this study indicate for the first time, that Bz reduces the bone tumour burden, however further in-depth analysis into the molecular mechanisms by which this is occurring, is being performed (i.e., CD31 vessel analysis, Ob/Oc counts in contact with the tumour).



Where applicable, experiments conform with Society ethical requirements.

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