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Vitamin A pushes breast cancer to form blood vessel cells
Date:7/15/2008

ers demonstrated that treating the cells with RA turns on 81 genes that are associated with endothelial cells, such as vascular endothelial (VE) cadherin, which plays a role in binding endothelial cells together into a structure. When they then mixed the treated cancer cells with endothelial cells taken from human umbilical cord blood, structures similar to blood vessels developed within the tumor masses grown in culture.

This makes sense, says Byers, because vitamin A is known to be necessary for embryonic development precisely because it helps to "differentiate" stem cells, pushing them to become required tissue. In the same way, taking too much vitamin A can result in birth defects.

So, in cancer cells, vitamin A seems to be turning on cancer stem cells, allowing them to form the blood vessel tissue -- needed most as tumors develop. Independent formation of these vessels is what has been proposed in the vasculogenic mimicry theory, developed by Mary Hendrix, , Ph.D., of Northwestern University, Byers says.

"Like many scientists, I was not an advocate of this notion because it seemed too far fetched, but now, based on these findings and my years of working on retinoids and breast cancer, I am a believer," he says. "And what this study tells us is that treating stem cells that have retained the ability to become cell types other than breast with differentiating agents such as vitamin A may cause an inappropriate cell to develop - in this case potentially promoting tumor vasculogenesis and growth, which is not a desired effect."

While there is much work yet to do to further define the molecular mechanisms by which endothelial cells form within tumors and assemble themselves into blood vessels, Byers says that these findings open a new door to drug development. "Cancer drugs based on stopping host-derived angiogenesis have met with mixed success, and we think there could be new ways to target and halt the ability of tumor cells th
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Contact: Karen Mallet
km463@georgetown.edu
414-312-7085
Georgetown University Medical Center
Source:Eurekalert

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