Key Protein in Blood Vessel Formation Found

Could help fight against heart disease, cancer

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HealthDay Reporter

WEDNESDAY, April 14, 2004 (HealthDayNews) -- The discovery of a protein that plays a critical role in the formation of blood vessels could lead to more effective treatments for heart disease and cancer, researchers report.

The protein, designated Egfl7, guides the newly born cells that will become blood vessels as they form the required tubular structure, a group led by Weilan Ye, a scientist at the biotechnology company Genentech Inc., reports in the April 15 issue of Nature.

"We have known that there are many factors that control the generation of the cells that are the building blocks of blood vessels," Ye said. "This adds knowledge about how those building blocks are put together to form the magnificent plumbing system called the vascular system."

That knowledge could help in heart disease, where "we would like to repair blood vessels," Ye said. "Without understanding how the blood vessels are put together, that would not be practical."

In cancer, the goal would be to prevent the formation of blood vessels that a tumor needs to grow. The attack against this process of angiogenesis, proposed several years ago by Dr. Judah Folkman of Harvard University, has centered on ways to prevent production of cells that will form blood vessels, Ye explained.

"In many cases, preventing their production is not possible," she said. "Now we might prevent them from doing the right thing as they try to form blood vessels. It is another way of blocking angiogenesis at a different stage."

Egfl7 is produced early in the life of the cells that will form blood vessels, she said. It plays its role as they begin to maneuver, guiding them into formation of the desired tubular structure.

"Usually, most cells in the body are not moving around a lot," she said. "These cells want to move around and align into a tubular formation, so they secrete this protein."

Cells usually stop making the protein in most parts of the body after the blood vessels have been built. In adult mice, there is some limited production only in organs that require a large blood supply, such as the lungs, heart and kidneys.

But there is a significant exception to that rule, Ye said: "In tumors, this gene is turned on again." Lacking that activity, a cancer would not have the blood supply it needs for its relentless growth.

Ye and her colleagues already have developed antibodies that interfere with the activity of Egfl7. "We are testing them in tumors to see if we can prevent the tube from being made," she said.

The finding "represents an important step towards understanding of vessel assembly," said Tao P. Zhong, an assistant professor of medicine and cell biology at Vanderbilt University Medical Center, who has done research on blood vessel formation.

Previous studies have found "very few molecules" involved in the formation of tubular blood vessel structures, Zhong said.

"I believe that determining the mechanisms of Egfl7 and its potential signaling pathways may help to unravel potential therapeutic approaches in cancer and cardiovascular disease," he said.

More information

Learn more about the formation of blood vessels from the American Heart Association or the National Cancer Institute.

SOURCES: Weilan Ye, Ph.D., scientist, Genentech Inc., South San Francisco, Calif.; Tao P. Zhong, Ph.D., assistant professor of medicine and cell biology, Vanderbilt University Medical Center, Nashville, Tenn.; April 15, 2004, Nature

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