Effects of oestradiol and tamoxifen on VEGF, soluble VEGFR-1, and VEGFR-2 in breast cancer and endothelial cells
Effects of oestradiol and tamoxifen on VEGF, soluble VEGFR-1, and VEGFR-2 in breast cancer and endothelial cells
S. Garvin, U.W. Nilsson, and C. Dabrosin
Division of Gynecologic Oncology, University Hospital, SE-581 85 Linko¨ping, Sweden
British Journal of Cancer (2005) 93, 10005-1010. Published online 18 October 2005.
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Summary
This paper sought to discover the relation between cancer and endothelial cells and the effect of oestradiol and tamoxifen on both types of cells. Vascular endothelial growth factor (VEGF) is a key mediator of tumor angiogenesis, which includes neovascularisation in human breast cancer, and acts via two tyrosine kinase receptors VEGFR-1 and VEGFR-2. Oestradiol has been proven to increase levels of VEGF while tamoxifen inhibits the secretion of VEGF in breast cancer in vivo. Ratio of sVEGFR-1 to VEGF is a strong indicator of disase-free and overall survival in breast cancer patients.
Results indicated that oestradiol decreased secreted sVEGFR-1, increased secreted VEGF, and decreased the ratio of sVEGFR-1/VEGF in MCF-7 human breast cancer cells. Addition of tamoxifen significantly countered the effects of oestradiol. Additionally, tamoxifen and oestradiol exert dual effects on the angiogenic environment in breast cancer by regulating cancer cell-secreted angiogenic ligands (e.g. VEGF and sVEGFR-1) and by affecting VEGFR-2 expression of endothelial cells.
Significance
Breast cancer is one of the most common forms of cancer in women and one of the leading causes of cancer death. This study demonstrates the advances being made to better understand the linkage between breast cancer cells' individual molecular components, oestradiol, and tamioxifen. It is an example of the use of tissue engineering as it attempts to better understand the principles of breast cancer cell growth. Application of results can be used to develop therapeutic strategies aimed at replacement and repair of tumor cells. In this case, combination of tamoxifen and oestradiol delivered to breast tumor cells is a viable solution that should be further explored to eliminate or reduce breast cancer.
My lab group is interested in conducting an experiment based on the understanding of oestradiol's relationship with MCF-7 breast cancer cells and VEGF secretion to determine gene expression and optimal VEGF secretion rate. This paper is a valuable resource as it gives (1) a protocol and conditions to grow MCF-7 cells and (2) amount of oestradiol that can be added to physiologically mimic local production and accumation of oestradiol in human breast tumors in vivo. Additionally, this paper's reference section will serve as additional resources for exploration.
5 comments:
The use of MCF7 cells and endothelial cells to study the effect of oestradiol and tamoxifen is very interesting. However, it is unclear to me which cells were injected into the mice and how this in vivo data was interpreted and analyzed. Were the mice injected with endothelial cells or MCF7-tumor inducing cells? And how does the in vivo data compare to the in vitro data?
I read your original paper and found out that sVEGFR-1 is a naturally occurring soluble form of VEGFR-1 and is thought to be a crucial negative regulator of VEGF in breast cancer (since you did not explain that in your summary). Our team is interested in the vitro experiment they did in MCF-7 cells. I feel jealous that their results show estradiol(E2) significantly increased secreted VEGF.
Ok. Here some differences between their experiment and our experiment.
1. They used MCF-7 ATCC strain. According to my paper, ATCC strain has an intermediate response to estradiol and while 7S strain is non-responsive to estradiol and NKI strain is most sensitive to estraiol. Because of time and budget limit, we ended up using unkown strain. Yet, we should use NKI strain in the future for better result.
2. They only used media with serum to seed cells for one day. Then, they used serum free estradiol solution to eliminate the possible VEGF contamination from serum. Cool…we have a good amount of serum in our estradiol solution…
3. They didn't bother to measure the VEGF until the day 7 and changed the estradiol solution every day. They used Petri dish so I bet they have to wait around 7 days until ~80% confluence and changing the estradiol solution every keep their very healthy. This way, they don’t have to deal with the fluctuation of in amount of VEGF amount in media over cell proliferation due to both secretion and deterioration. I know we decided to take samples each day to make sure we have enough data to analyze and keep the media because we expect the accumulation of VEGF over time will become detectable by dot blot. I think I painfully learned that time and money are always constrains for research…
Sorry for the long comment. But this is not question~~
hey, you have two posting??
I'm not very familiar with breast cancer experiments, so I don't really understand the procedure. So, they injected a pellet of cells into the mouse; did they remove MCF-7 cells from that same mouse? Does it matter where this pellet was injected? Was it in the breast tissue?
Just curious, but why did they use nude mice? Was it to avoid graft rejection or not mount a response against the tumor?
Sorry for the mistakes in statement3,
I think I fixed it in following...
3. They didn't bother to measure the VEGF until the day 7 and changed the estradiol solution every day. They used Petri dish so I bet they have to wait around 7 days until ~80% confluence and changing the estradiol solution every day keep their cells very healthy. This way, they don’t have to deal with the fluctuation in amount of VEGF in media over cell proliferation due to both secretion and deterioration of VEGF. I know we decided to take samples each day to make sure we have enough data to analyze and keep the media because we expect the accumulation of VEGF over time will become detectable by dot blot. I think I painfully learned that time and money is always constrains for research…
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