( during menstruation pregnancy or ti...)NCI Researchers Discover Genes That Are Turned on at High Levels in,Tumor-associated Blood Vessels of Mice and Humans,Health

The NCI research team, led by Brad St. Croix, Ph.D., head of the Tumor Angiogenesis Section at the NCI's Center for Cancer Research (CCR) in Frederick, Md., set out to discover the molecular differences between tumor-associated and normal angiogenesis to identify potential new drug targets. St. Croix and his colleagues focused on endothelial cells, which line the inner surface of blood vessels and are critical for new vascular growth.

The researchers chose to analyze endothelial cells derived from mouse liver, because the liver can be induced to sprout new blood vessels when regenerating itself following partial surgical removal. By comparing the gene expression profiles of endothelial cells from regenerating liver to those derived from tumor-bearing livers, the researchers found 13 distinct genes that were selectively overexpressed (turned on to a greater degree than other genes) during disease-related angiogenesis. Among the genes identified was CD276, a gene that encodes a protein located on the cell surface, as well as other known and previously undescribed genes.

To determine if the mouse findings were relevant to human cancers, the researchers then examined CD276 expression patterns in endothelial cells derived from cancer patients. They found that the CD276 protein was overexpressed in tumor-associated blood vessels from colon, lung, breast, esophageal and bladder cancers. In addition, the protein was also found to be frequently overexpressed by the tumor cells themselves, indicating that a suitable inhibitory molecule might be able to deliver a double blow -- one to the tumor cells themselves and the other to the blood vessels that feed them.

"These studies demonstrate that CD276 is overexpressed in the blood vessels of a variety of human cancers," says S
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