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Tamoxifen inhibits angiogenesis in estrogen receptor-negative animal models.

Publication ,  Journal Article
Blackwell, KL; Haroon, ZA; Shan, S; Saito, W; Broadwater, G; Greenberg, CS; Dewhirst, MW
Published in: Clin Cancer Res
November 2000

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 x 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.

Duke Scholars

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

November 2000

Volume

6

Issue

11

Start / End Page

4359 / 4364

Location

United States

Related Subject Headings

  • Tamoxifen
  • Receptors, Estrogen
  • Rats, Inbred F344
  • Rats
  • Oncology & Carcinogenesis
  • Models, Animal
  • In Vitro Techniques
  • Fibrosarcoma
  • Female
  • Estrogen Receptor Modulators
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Blackwell, K. L., Haroon, Z. A., Shan, S., Saito, W., Broadwater, G., Greenberg, C. S., & Dewhirst, M. W. (2000). Tamoxifen inhibits angiogenesis in estrogen receptor-negative animal models. Clin Cancer Res, 6(11), 4359–4364.
Blackwell, K. L., Z. A. Haroon, S. Shan, W. Saito, G. Broadwater, C. S. Greenberg, and M. W. Dewhirst. “Tamoxifen inhibits angiogenesis in estrogen receptor-negative animal models.Clin Cancer Res 6, no. 11 (November 2000): 4359–64.
Blackwell KL, Haroon ZA, Shan S, Saito W, Broadwater G, Greenberg CS, et al. Tamoxifen inhibits angiogenesis in estrogen receptor-negative animal models. Clin Cancer Res. 2000 Nov;6(11):4359–64.
Blackwell, K. L., et al. “Tamoxifen inhibits angiogenesis in estrogen receptor-negative animal models.Clin Cancer Res, vol. 6, no. 11, Nov. 2000, pp. 4359–64.
Blackwell KL, Haroon ZA, Shan S, Saito W, Broadwater G, Greenberg CS, Dewhirst MW. Tamoxifen inhibits angiogenesis in estrogen receptor-negative animal models. Clin Cancer Res. 2000 Nov;6(11):4359–4364.

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

November 2000

Volume

6

Issue

11

Start / End Page

4359 / 4364

Location

United States

Related Subject Headings

  • Tamoxifen
  • Receptors, Estrogen
  • Rats, Inbred F344
  • Rats
  • Oncology & Carcinogenesis
  • Models, Animal
  • In Vitro Techniques
  • Fibrosarcoma
  • Female
  • Estrogen Receptor Modulators