WASHINGTON -- An enzyme that normally powers cells has been found to also promote the growth of blood vessels that feed tumors, a discovery researchers say could lead to new drugs to fight cancer.
Dr. Salvatore V. Pizzo, co-author of the study by Duke University researchers, said that without the energy supplied by the enzyme ATP synthase, tumors would not grow beyond the size of a pinhead because they could not develop the blood vessels needed to receive nutrients.ATP normally resides inside cells, but Pizzo said his group was startled to find the energy packet on the surfaces of cells lining blood vessels. Their findings were reported Tuesday in the Proceedings of the National Academy of Sciences.
Researchers in many labs recently have been studying the growth of blood vessels that supply cancer tumors with oxygen and nutrients, searching for possible ways to shut off that blood vessel growth.
The research intensified after Dr. Judah Folkman of Children's Hospital in Boston showed that a compound he isolated from the blood, angiostatin, was able to stop tumor growth in mice by blocking the formation of blood vessels.
A number of compounds that can block blood vessel formation have been discovered. In fact, a separate paper in the same National Academy of Sciences publication Tuesday reports on isolating such a substance from cartilage.
But exactly how angiostatin and similar compounds work has not been known. The Duke discovery may be the answer.
"Until now, people knew that angiostatin blocked blood vessel growth, but there was no obvious mechanism," said Pizzo. "Now we know why it works."
The study "is a big jump ahead ... because it identifies a protein that binds (attaches to) angiostatin" and suggests how angiostatin prevents blood vessel growth, Folkman said. The discovery puts researchers on track to isolate a compound from angiostatin that could work more directly to block blood vessel formation, he said.
The discovery of ATP on the surface of endothelial cells, the lining of blood vessels, came as a surprise, said Pizzo. The enzyme was previously found only inside cells.
"ATP is what the cells use as a fuel, as an energy source," said Pizzo. "It is present inside the cell, in the mitochondria, and is the little energy factory for the cell."
The enzyme apparently is activated when the blood's oxygen content is lowered. Nature may have designed ATP as a healing mechanism, to build new vessels so the body can repair tissue damaged by injury or disease, Pizzo said.
"Tumors are that way," he said. "Tumors tend to take advantage of a normal mechanism in the body and then exaggerate it to their own growth advantage."
When tumors do form, cells in the center of the growth are deprived of oxygen. That may trigger the formation and action of ATP, said Pizzo.
With a better understanding of how ATP causes blood vessels to grow, researchers also might be able to use the enzyme to promote beneficial blood vessel growth, such as in heart disease or diabetes, Pizzo said.