Block a Protein, Starve a Tumor

By Jamie Murphy

When a malignant tumor sets up camp somewhere in the human body, it requires a generous supply of blood in order to survive and grow. Cancer cells secure this supply by somehow encouraging angiogenesis, the proliferation of networks of tiny capillaries, which connect the incipient tumor to nearby arteries and veins. But what are the signals that entice the blood vessels to leave their established pathways and converge on a tumor? Scientists have sought the answer to that question for years. If such signals could be blocked, they reasoned, the tumor would no longer grow.

At Harvard Medical School last week, Bert Vallee, 66, a professor of biochemical sciences, announced a major breakthrough in the study of angiogenesis. Vallee and his associates, together with scientists at the University of Washington, in Seattle, revealed that they had isolated and purified a protein that promotes angiogenesis. More important, they had cloned the protein's gene, a step that could ultimately enable scientists to produce the substance in large and pure quantities. While other angiogenic factors have been identified in the past, their genes have never been cloned.

The protein, which the Harvard team named angiogenin, was isolated from human colon-cancer cells after a decade-long search financed by a grant from Monsanto. What partly slowed the quest was the fact that the protein is found in the body in only minuscule quantities. Even so, says Team Member James Riordan, angiogenin is so potent that it can induce blood vessels to form when it is present in tissue as only one part per quadrillion.

Vallee's work was instantly hailed as a major step by Judah Folkman, a cancer researcher at Harvard who pioneered the study of angiogenesis. The prospect of learning to control the proliferation of blood vessels, Folkman says, has ! broad implications in the treatment not only of cancer but of many human ailments. For example, angiogenin might someday be used to encourage the growth of new blood vessels in and around the heart after a heart attack. Stimulating the growth of capillaries would also speed recovery from burns and other types of tissue damage.

By blocking angiogenin, on the other hand, doctors might not only stop the growth of tumors but perhaps prevent blindness in diabetics, a complication that results from the abnormal growth of capillaries in the retina. A possible bonus: tests for angiogenin in the blood or urine could provide early warnings of cancer.

Vallee cautions, however, that such applications are a long way off and that many basic questions must first be answered. While angiogenin is "cardinal to the process" of blood-vessel formation, he says, the protein is different from other known angiogenic factors that may work at different stages of the process. If so, controlling excessive blood-vessel growth in patients with cancer or other ailments could prove to be a complicated business. In any case, the next step for researchers will be to produce enough angiogenin for study. Right now, Vallee has no more than 100 micrograms (.0000035 oz.) of the precious substance, but he hopes to use either genetically engineered bacteria or yeast to produce more of it before long. Although research with angiogenin is just beginning, he says, "the potential boggles the mind."

With reporting by Sue Wymelenberg/Boston