Posted on 06/18/2004 11:09:05 PM PDT by TigerLikesRooster
Tumor-Starving Protein Identified
By Karen Pallarito
HealthDay Reporter
FRIDAY, June 18 (HealthDayNews) -- Researchers in Colorado say they have identified a protein that thwarts the growth of new blood vessels that feed and enlarge tumors.
The protein, called fibulin-5, occurs naturally in the body, but researchers say a slightly altered version proved even more effective in arresting blood vessel growth.
The protein works by choking off the nutrient and oxygen supply to tumors, preventing the cancer from growing and spreading to other parts of the body. Researchers believe it could one day be developed as a drug to treat cancer patients.
If further testing bears out its effectiveness, fibulin-5 may join an emerging class of drugs that inhibit angiogenesis, the sprouting of new blood vessels.
"If you can block angiogenesis, you can essentially starve a tumor," explained William P. Schiemann, assistant professor in the cell biology program at National Jewish Medical and Research in Denver and a co-author of the paper, which appears in the June issue of the journal DNA and Cell Biology.
Since the protein can be detected in blood serum and urine, it may also serve as a useful marker in diagnosing cancer status, said Emmanuel Hilaire, a technology transfer specialist at National Jewish.
If fibulin-5 is dropping, it might signal a tumor is preparing to grow or spread, he explained. "You should be able to detect that difference by developing a diagnostic kit."
Harvard University's Dr. Judah Folkman, whose pioneering research in angiogenesis has spawned a booming field of laboratory investigation, said the article is very important because of its many, rather immediate implications.
The study will likely garner great interest, Folkman believes, since it's the first to demonstrate the anti-angiogenic effects of fibulin-5.
"This paper announces a new direction in which many labs may want to follow up immediately," he asserted.
Fibulin-5, a member of a family of proteins that regulate tissue development and repair, interacts with endothelial cells, which are specialized cells that are capable of forming new blood vessels.
To spur new blood vessel growth, cancer cells release special molecules signaling angiogenesis to begin. One of them is called vascular endothelial growth factor (VEGF).
Schiemann and postdoctoral fellow Allan R. Albig wanted to know more about fibulin-5's function. "We approached it with the hypothesis that it's likely regulating some aspect of angiogenesis," Schiemann said.
In cell cultures, the authors showed fibulin-5 levels plummet when endothelial cells begin to form blood vessels. High levels of the protein, they discovered, could prevent new blood vessel growth by frustrating the ability of endothelial cells to move and proliferate.
The study showed that fibulin-5 inhibits blood vessel growth in two ways. For one, it tells the endothelial cells to pay no attention to the incoming pro-angiogenic factor VEGF. Simultaneously, it boosts levels of thrombospondin-1, a naturally occurring protein that can inhibit angiogenesis.
"It prevents acceleration and puts on the brakes," Folkman said. "It's unusual to see a single molecule do two things like that."
The fibulin-5 discovery also may have applications in clinical areas other than cancer. As an example, Folkman cites a 1999 mouse study led by Harvard's Dr. Karen Moulton, an instructor in surgery, showing that the angiogenesis inhibitor endostatin significantly reduced plaque buildup.
Since fibulin-5, like endostatin, is found in the walls of the arteries, "It raises the speculation of whether atherosclerotic plaques have a fibulin deficiency," Folkman said.
In February, the U.S. Food and Drug Administration approved Avastin, a treatment for colorectal cancer and the first drug to choke tumor growth by preventing new blood vessels from forming.
But the scientific quest for the next angiogenesis inhibitor is in full throttle. In the United States, roughly 30 angiogenesis inhibitors are being tested and about 62 different trials are being conducted, Folkman said. Worldwide, at least 50 agents that block blood vessel growth are being tested, he said.
"I think it's important that in order to really develop effective therapies that you're going to have to come at these problems from more than one direction," Schiemann said. "I think you greatly increase your chances of success."
How about some clinical trials via an airburst of this stuff over Washington D.C.?
Better yet, how about spraying on Riyadh, Teheran's, Damascus, and the last but not the least Pyongyang?:)
Liberals in government won't support it! ; )
That's interesting.
Thanks for posting this article.
Whatever happened to Angiostatin? This sounds quite similar, and the former has been in limited human trials for the last couple of years. I'm no doctor, are they one and the same?
Sounds like more trolling-for-grants.
Not at all. An early article about the problem is "The Vascularization of Tumors", Scientific American, May, 76. Tumors release a special substance that causes blood vessels to grow in them. (Otherwise, they'd starve)
How much do you want to bet that if all the money dumped into an AIDS cure is instead diverted to finding the cure for cancer we would have the antidote by now?
Slowly, Judah Folkman is curing many kinds of cancer. Starving the tumors of blood will prove to be the best way to remove them and will spare the already weakened patient the rigors of surgery. BY reducing the body's ability to produce new blood vessles in new growths new cancers will not get started helping to reduce the rate of metastasis. The man's a genius.
Bump
I don't know the man personally but know quite a few people who do. They say he is one of the nicest and one of the smartest men they've ever worked with.
Yup. And Folkman was the author of the Sci-Am piece I mentioned, but I don't think he was at Harvard then.
That is such hopeful news. One day, this will be the treatment of choice for cancer patients. How long will it take?
bump
I wish I knew. It wasn't in time for my wife who died in March but our daughter felt a special pride in the the trying.
Muir,
My condolences to you. How very sad for you and your daughter. I hope you have a good friend or two to help you through.
The Westerner
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