Tamoxifen inhibits angiogenesis in estrogen receptor-negative animal models

Inhibition of tumor angiogenesis is a therapeutic strategy that can inhibit tumor growth and metastases, The aim of this study was to determine whethe r the estrogen receptor (ER) ligand drug tamoxifen has antiangiogenic effec ts. We used three different models of angrogenesls, including measurement o f microvessel densities in murine tumors, ex vivo aortic ring assays, and c orneal pocket assays. ER-negative fibrosarcoma tumors In tamoxifen-treated ovariectomized rats had significantly less vessel formation compared with u ntreated animals (median microvessel density, 53.6 versus 94.3 counts/per x 200 field; P = 0.002), Rat aortic rings treated with tamoxifen at several d ifferent concentrations demonstrated significantly less vascular sprouting than control rings (P = 0.0001). Corneal pocket assays performed in tamoxif en-treated rats compared with control and estrogen-treated rats demonstrate d decreased vascular length (0.88 mm versus 1.26 mm,versus 1.47 mm; P = 0.0 22) and vessel area (21% versus 34% versus 47%; P = 0.018), These three ani mal models all showed significant inhibition of angiogenesis by tamoxifen a nd suggest a possible contributory mechanism of ER-independent manipulation by tamoxifen in the treatment and prevention of breast cancer. These studi es raise the question as to whether or not newer ER ligand drugs might poss ess even more potent antiangiogenic effects, which in turn could lead to th e broadening of the clinical usefulness of these compounds in a number of d iseases. More importantly, these studies suggest that the antiangiogenic ef fects of tamoxifen are due, in part, to ER-independent mechanisms.