DURHAM, N.C. -- Duke University Medical Center researchers believe they have answered one of cancer's central enigmas: why some blood vessels are able to grow to, and feed, tumors, while other vessels are not. In the March 16 issue of the Proceedings of the National Academy of Science, the scientists report the blood protein angiostatin, which is known to stop the growth of new blood vessels to tumors, works by depleting the chemical energy that blood vessel cells need to grow.
To do this, angiostatin latches on to and inhibits ATPsynthase, an enzyme that provides chemical energy for the cell. Without that energy, blood vessels cannot grow to the site of a tumor, and without the nutrient supply in blood, tumors cannot grow larger than a pinhead.
Conversely, when unchecked by angiostatin, ATPsynthase provides a generator of sorts to blood vessels so that they can survive in the atmosphere of cell death caused by cancer. Cancer researchers have long wondered how these vessels stay vigorous enough to continue to grow to and feed tumors.
Lead scientists Dr. Sal Pizzo and Tammy Moser said the discovery is "startling" because the ATPsynthase enzyme has never before been found on the surface of endothelial cells, which are the cells that line blood vessels.
In fact, ATPsynthase has not been known to exist outside of a cell body. It has only been found within a mitochondria, a sac-like structure which acts as a cell's chemical powerhouse.
"It was surprising to see ATPsynthase on blood vessel cells because it was never expected there," said Pizzo in an interview. "But it makes perfect biological sense, and it's terribly exciting."
The finding offers both theoretical as well as practical implications, Pizzo said. It offers a novel insight into the body's use of ATPsynthase as "power packs" in situations where energy is depleted. And it suggests a new route to developing drugs that block angiostatin.