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Novel Biological Interaction Found To Explain Blood Vessel Growth To Tumors

uent tumors will come back quickly and spread, seeding the body with deadly fast-growing tumors.

A decade ago, Folkman proposed that tumors themselves regulate the growth of blood vessels. One notion was that tumors could produce proteins that would travel through the bloodstream, preventing vessels from growing to any new cancer metastasis. This idea explains what has been observed, although no one understands why a tumor would exert such control, or why only some tumors work in this way.

Folkman's lab later found the substance that inhibits blood vessel growth. It was a small piece of a large and common blood protein called plasminogen, which is involved in blood clotting. He called this protein "angiostatin," and demonstrated it was involved in "anti-angiogenesis" -- stopping the process of new blood vessel growth.

Folkman then showed in animal experiments that injections of the angiostatin protein stopped tumors from growing, and efforts have been underway in the last year to produce a drug for human cancer therapy based on the angiostatin molecule.

Pizzo and Moser set out to study what happened when angiostatin "bound" on the surface of endothelial cells. They looked for where angiostatin's "key" fit into the cellular "lock" that then shut down vessel growth.

Since plasminogen is known to bind to a protein called annexin II on endothelial cells, they expected to find that angiostatin bound to same site. After several years of gathering material and analyzing data, Moser found a different molecule, which she identified by mass spectrometry as ATPsynthase. Moser then tested her findings by introducing an antibody to ATPsynthase that would block the action between angiostatin and endothelial cells. Indeed, she found the antibody blocked angiostatin's ability to inhibit proliferation by 90 percent.

The researchers stressed that while there is still much to learn about how angiostatin regulates blood vessel growth, there are now many n
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Contact: Renee Twombly
Twomb001@mc.duke.edu
919-684-4148
Duke University Medical Center
16-Mar-1999


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