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 whether the estrogen receptor (ER) ligand drug tamoxifen has antiangiogenic effects. We used three different models of angiogenesis, including measurement o...

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Published in:	Clinical cancer research Vol. 6; no. 11; pp. 4359 - 4364
Main Authors:	BLACKWELL, Kimberly L, HAROON, Zishan A, SIGING SHAN, SAITO, Willfred, BROADWATER, Gloria, GREENBERG, Charles S, DEWHIRST, Mark W
Format:	Journal Article
Language:	English
Published:	Philadelphia, PA American Association for Cancer Research 01-11-2000
Subjects:	Angiogenesis Inhibitors - pharmacology Animals Antineoplastic agents Aorta - drug effects Biological and medical sciences Breast Neoplasms - drug therapy Chemotherapy Cornea - drug effects Estrogen Receptor Modulators - pharmacology Female Fibrosarcoma - blood supply In Vitro Techniques Medical sciences Models, Animal Pharmacology. Drug treatments Rats Rats, Inbred F344 Receptors, Estrogen - analysis Tamoxifen - pharmacology Antineoplastic agent Animal model Cornea Rat Sarcoma Rodentia Estrogen Fibrosarcoma Malignant tumor Tamoxifene Angiogenesis Vertebrata Chemotherapy Mammalia Treatment Animal Aorta Antiangiogenic agent Non steroid compound Hormonal receptor
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Summary:	Inhibition of tumor angiogenesis is a therapeutic strategy that can inhibit tumor growth and metastases. The aim of this study was to determine whether the estrogen receptor (ER) ligand drug tamoxifen has antiangiogenic effects. We used three different models of angiogenesis, including measurement of microvessel densities in murine tumors, ex vivo aortic ring assays, and corneal pocket assays. ER-negative fibrosarcoma tumors in tamoxifen-treated ovariectomized rats had significantly less vessel formation compared with untreated animals (median microvessel density, 53.6 versus 94.3 counts/per× 200 field; P = 0.002). Rat aortic rings treated with tamoxifen at several different concentrations demonstrated significantly less vascular sprouting than control rings ( P = 0.0001). Corneal pocket assays performed in tamoxifen-treated rats compared with control and estrogen-treated rats demonstrated decreased vascular length (0.88 mm versus 1.26 mm versus 1.47 mm; P = 0.022) and vessel area (21% versus 34% versus 47%; P = 0.018). These three animal models all showed significant inhibition of angiogenesis by tamoxifen and suggest a possible contributory mechanism of ER-independent manipulation by tamoxifen in the treatment and prevention of breast cancer. These studies raise the question as to whether or not newer ER ligand drugs might possess even more potent antiangiogenic effects, which in turn could lead to the broadening of the clinical usefulness of these compounds in a number of diseases. More importantly, these studies suggest that the antiangiogenic effects of tamoxifen are due, in part, to ER-independent mechanisms.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1078-0432 1557-3265