UCSD discovery opens new avenues for design of anti-tumor medications

The response of blood vessels to low oxygen levels may be the Achilles' heel of a developing tumor, according to a study led by University of California, San Diego biologists.

The study, published in the November 15 issue of the journal Cancer Cell, is the first to examine how blood vessels respond to the low oxygen conditions that result from the presence of a growing tumor. Previous work by the UCSD group and others has shown that tumors, which need a blood supply to provide oxygen and nutrients, release chemical signals that summon the blood vessels to grow toward them.

However, these latest findings show that the blood vessels themselves are actively responding to oxygen levels, not just to the signals sent by the tumor. According to the researchers, developing drugs that interfere with the blood vessels' response to low oxygen may be a potent anti-tumor strategy.

"We show that the blood vessels' response to lack of oxygen is just as important as the response of cancer cells to lack of oxygen," said Randall Johnson, a professor of biology at UCSD who headed the research team. "We identified a gene that turns on in the cells lining blood vessels when they are not getting enough oxygen and showed that without this gene the blood vessels cannot grow to nourish the developing tumor. Drugs that interfere with this gene, or another gene involved in the blood vessels' response, should block tumor growth."

The researchers showed that the gene, HIF-1alpha, is normally turned off in endothelial cells--the cells lining blood vessels. But when the endothelial cells are exposed to low oxygen conditions, such as those generated when a tumor is using up the oxygen supply, the gene becomes activated. By switching on other genes, HIF-1alpha causes the endothelial cells to proliferate and migrate.

In mice lacking HIF-1alpha in endothelial cells, blood vessels failed to grow to the tumors. Without blood vessels, the tum

Contact: Kim McDonald
University of California - San Diego

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