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In vivo measurement of tumor estradiol and Vascular Endothelial Growth Factor in breast cancer patients
Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
2008 (English)In: BMC Cancer, ISSN 1471-2407, Vol. 73, no 8Article in journal (Refereed) Published
Abstract [en]

Background: Angiogenesis, crucial for tumor progression, is a process regulated in the tissue micro-environment. Vascular endothelial growth factor (VEGF) is a potent stimulatory factor of angiogenesis and a negative prognostic indicator of breast cancer. VEGF is biologically active in the extracellular space and hitherto, there has been a lack of techniques enabling sampling of angiogenic molecules such as VEGF in situ. The majority of breast cancers are estrogen-dependent, and estrogen has been shown to regulate VEGF in normal breast tissue and experimental breast cancer. We investigated if microdialysis may be applicable in human breast cancer for sampling of extracellular VEGF in situ and to explore if there is an association with local estradiol and VEGF levels in normal and cancerous breast tissue.

Methods: Microdialysis was used to sample VEGF and estradiol in tumors and adjacent normal breast tissue in postmenopausal breast cancer patients. VEGF and estradiol were also measured in plasma, and immunohistochemical staining for VEGF was performed on tumor sections.

Results: We show that in vivo levels of extracellular VEGF were significantly higher in breast cancer tumors than in normal adjacent breast tissue. There was a significant positive correlation between estradiol and extracellular VEGF in normal breast tissue. However, no correlation was detected between estradiol and VEGF in tumors or between tumor VEGF and plasma VEGF.

Conclusion: We conclude that VEGF and estradiol correlates significantly in normal breast tissue. Microdialysis may be used to provide novel insight in breast tumor biology and the regulation of molecules in the extracellular space of human breast tumors in vivo.

Place, publisher, year, edition, pages
2008. Vol. 73, no 8
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-13940DOI: 10.1186/1471-2407-8-73OAI: oai:DiVA.org:liu-13940DiVA: diva2:22268
Available from: 2006-08-29 Created: 2006-08-29 Last updated: 2009-04-28
In thesis
1. Effects of sex steroids and tamoxifen on VEGF in the breast
Open this publication in new window or tab >>Effects of sex steroids and tamoxifen on VEGF in the breast
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Sex steroid exposure constitutes a risk factor for breast cancer, but little is known about the effects of sex steroids on factors mediating angiogenesis, the development of new blood vessels, in normal and malignant breast tissue. In this thesis we have investigated the effects of estradiol, progesterone, and the nonsteroidal anti-estrogen tamoxifen on vascular endothelial growth factor (VEGF) and its receptors (VEGFR-1 and VEGFR-2) in normal human breast tissue, endothelial cells, and breast cancer. We have applied the technique of microdialysis to provide in situ sampling of estradiol and VEGF in tumors and normal breast tissue of breast cancer patients in vivo. Furthermore, we present a novel method of culturing normal human breast tissue ex vivo.

Our results suggest a pro-angiogenic effect of estradiol and an anti-angiogenic effect of tamoxifen in the breast. Estradiol increased extracellular levels of VEGF in normal human breast tissue and breast cancer cells in vitro. In addition, estradiol decreased sVEGFR-1 in breast cancer cells and indirectly increased VEGFR-2 in endothelial cells. Compared to estradiol treatment alone, estradiol + tamoxifen increased sVEGFR-1 and decreased VEGF in breast cancer cells in vitro. Furthermore, estradiol + tamoxifen decreased tumor VEGF levels and tumor vasculature in human breast cancer xenografts in vivo. In breast cancer patients, a significant correlation was found between in vivo levels of estradiol and VEGF sampled by microdialysis in normal human breast tissue, suggesting that estradiol may be a potent regulator of VEGF in the breast in vivo. Tumor levels of VEGF were significantly higher than in normal breast tissue in vivo, supporting the role of VEGF in tumor angiogenesis. For studies of normal human breast, whole breast tissue may be cultured in vitro for up to one week with preserved morphology. Using this method, estradiol, and not progesterone, appears to be the main sex steroid regulator of extracellular VEGF in normal breast tissue. In conclusion, the data suggest that sex steroids and tamoxifen exert pro- and anti-angiogenic effects in normal breast tissue and breast cancer.

Place, publisher, year, edition, pages
Institutionen för biomedicin och kirurgi, 2006
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 953
Keyword
angiogenesis, breast cancer, estradiol, MCF-7, microdialysis, nude mice, progesterone, sVEGFR-1, VEGFR-2
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-7230 (URN)91-85497-91-6 (ISBN)
Public defence
2006-09-22, Berzeliussalen, Faculty of Health Sciences, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2006-08-29 Created: 2006-08-29 Last updated: 2009-08-22

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Garvin, StinaDabrosin, Charlotta

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