Effects of estradiol and tamoxifen on VEGF, soluble VEGFR-1, and VEGFR-2 in breast cancer and endothelial cells
2005 (English)In: British journal of cancer, ISSN 0007-0920, Vol. 93, no 9, 1005-1010 p.Article in journal (Refereed) Published
Angiogenesis is regulated by the balance between pro- and antiangiogenic factors. Vascular endothelial growth factor (VEGF), acting via the receptors VEGFR-1 and VEGFR-2, is a key mediator of tumour angiogenesis. The soluble form of the VEGF receptor-1 (sVEGFR-1) is an important negative regulator of VEGF-mediated angiogenesis. The majority of breast cancers are oestrogen dependent, but it is not fully understood how oestrogen and the antioestrogen, tamoxifen, affect the balance of angiogenic factors. Angiogenesis is a result of the interplay between cancer and endothelial cells, and sex steroids may exert effects on both cell types. In this study we show that oestradiol decreased secreted sVEGFR-1, increased secreted VEGF, and decreased the ratio of sVEGFR-1/VEGF in MCF-7 human breast cancer cells. The addition of tamoxifen opposed these effects. Moreover, human umbilical vein endothelial cells (HUVEC) incubated with supernatants from oestradiol-treated MCF-7 cells exhibited higher VEGFR-2 levels than controls. In vivo, MCF-7 tumours from oestradiol+tamoxifen-treated nude mice exhibited decreased tumour vasculature. Our results suggest that tamoxifen and oestradiol exert dual effects on the angiogenic environment in breast cancer by regulating cancer cell-secreted angiogenic ligands such as VEGF and sVEGFR-1 and by affecting VEGFR-2 expression of endothelial cells.
Place, publisher, year, edition, pages
2005. Vol. 93, no 9, 1005-1010 p.
breast cancer, flt-1, flk-1, KDR, MCF-7, nude mice
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-13939DOI: 10.1038/sj.bjc.6602824OAI: oai:DiVA.org:liu-13939DiVA: diva2:22267