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Here, we examined the impact of neutralizing tumor\u2010derived vascular endothelial growth factor (VEGF) in animal models of subcutaneous tumor growth and bone metastasis formation. Silencing of VEGF expression (Sh\u2010VEGF) in osteotropic human MDA\u2010MB\u2010231\/B02 breast cancer cells led to a substantial growth inhibition of subcutaneous Sh\u2010VEGF B02 tumor xenografts, as a result of reduced angiogenesis, when compared to that observed with animals bearing mock\u2010transfected (Sc\u2010VEGF) B02 tumors. However, there was scant evidence that either the silencing of tumor\u2010derived VEGF or the use of a VEGF\u2010neutralizing antibody (bevacizumab) affected B02 breast cancer bone metastasis progression in animals. We also examined the effect of vatalanib (a VEGF receptor tyrosine kinase inhibitor) in this mouse model of bone metastasis. However, vatalanib failed to inhibit bone metastasis caused by B02 breast cancer cells. In sharp contrast, vatalanib in combination with bevacizumab reduced not only bone destruction but also skeletal tumor growth in animals bearing breast cancer bone metastases, when compared with either agent alone. Thus, our study highlights the importance of targeting both the tumor compartment and the host tissue (<jats:italic>i.e<\/jats:italic>., skeleton) to efficiently block the development of bone metastasis. We believe this is a crucially important observation as the clinical benefit of anti\u2010angiogenic monotherapies in metastatic breast cancer is relatively modest.<\/jats:p>","DOI":"10.1002\/ijc.28787","type":"journal-article","created":{"date-parts":[[2014,2,18]],"date-time":"2014-02-18T15:50:51Z","timestamp":1392738651000},"page":"1319-1329","source":"Crossref","is-referenced-by-count":27,"title":["Combination of anti\u2010angiogenic therapies reduces osteolysis and tumor burden in experimental breast cancer bone metastasis"],"prefix":"10.1002","volume":"135","author":[{"given":"Richard","family":"Bachelier","sequence":"first","affiliation":[{"name":"INSERM, UMR 1033 F\u201069372 Lyon France"},{"name":"University of Lyon F\u201069622 Villeurbanne France"},{"name":"LabEx DEVweCAN F\u201069372 Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrille B.","family":"Confavreux","sequence":"additional","affiliation":[{"name":"INSERM, UMR 1033 F\u201069372 Lyon 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