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Genetic analysis of blood vessels and tumors hints at new targets for cancer therapy
By Bijal P. Trivedi

Researchers have completed an extensive study showing that blood vessels in human colon tumors differ significantly from those in normal colon tissue. Their findings may suggest a way to selectively destroy the blood supply that feeds the tumors, which would kill the cancer without affecting normal tissue repair and maintenance. The results are reported in the August 18 issue of Science.

A cross section of a brain tumor. On the right is the tumor (light blue) and on the left is normal brain tissue (dark blue). One gene (TEM7) only shows activity in tumor blood vessels (red).

Researchers at Johns Hopkins University, in Baltimore, Maryland, led by Bert Vogelstein and Kenneth Kinzler, focused on the endothelial cells, which line the inner surface of all blood vessels. They made a molecular library of all the genes that are active in colon tumor blood vessels and another for blood vessels from normal colon tissue. Together both libraries contained more than 32,500 genes. The comparison revealed 46 genes showing higher activity in tumor blood vessels, and 33 genes that showed very low activity.

Several of the 46 genes that are very active in colon tumor vessels have known functions such as making adhesive and scaffolding proteins that sit outside of the cell and lend structure to tissues and organs.

The researchers found that many genes showing heightened activity in colon tumor vessels are also active in pancreas, lung, breast and brain tumors, indicating that these patterns of gene expression seem to be characteristic of tumor blood vessels in general.

Not surprising, according to Brad St. Croix of Hopkins, is the finding that all the genes involved in tumor blood vessel formation but one are also active in other areas of normal blood vessel formation, such as the lining of the uterus during menstruation and in the tissue of healing wounds.

The researchers emphasize that this is a basic study and more research will be required to determine which genes can be used for diagnostic purposes and which would make good targets for cancer therapy.

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St. Croix, B. et al. Genes expressed in human tumor endothelium. Science 289, 1197-1202 (August 18, 2000).

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