Journal
CANCER LETTERS
Volume 292, Issue 1, Pages 32-40Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2009.11.002
Keywords
Estradiol; Sex steroids; Collagen; Microenvironment; Ascites
Categories
Funding
- Linkoping University Hospital
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There are several similarities between breast and ovarian cancer but anti-estrogen treatment is rarely used in ovarian cancer. We have previously shown that the most widely used anti-estrogen tamoxifen increased MMP-9 activity and endostatin generation in breast cancer. Here, we show that tamoxifen exposure of highly hormone responsive ovarian cancer cells decreased proliferation, and increased MMP-9 activity leading to increased levels of endostatin both in cell culture in vitro and in solid tumors of nude mice. Tamoxifen exposed tumors also exhibited significantly decreased tumor growth and vascularisation. Moreover, in ascites from ovarian cancer patients, MMP-9 was undetectable in majority of cases but a significant correlation of MMP-2 and endostatin was found. The effects on MMPs and endostatin generation are previously unknown mechanisms of estradiol and tamoxifen in ovarian cancer, which may have therapeutic implications in future anti-cancer options of hormone dependent ovarian cancer. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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