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Sympathetic-nerve fibers (green) are closely intertwined
with blood vessels (white) release norepinephrine that
stimulates vessel proliferation that fuels tumor growth.
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In a 2013 Science study the researchers led by Paul Frenette, professor of medicine and cell biology at Einstein, showed that nerves of the sympathetic nervous system, the flight or fight response nerves, promote tumor growth by producing norepinephrine, a chemical that gives a sudden boost to skeletal muscle contractions and rate and force of heart muscle contractions. The researchers found that norepinephrine binds to and stimulates receptors on tumor connective-tissue cells, helping the tumor to spread.
In the current study, also in Science, researchers used a mouse model of prostate cancer to how those connective tissue nerves drive tumor growth. They found that the particular cells bound line the inner surface of blood vessels. That binding triggers a "switch" that changes how the cells metabolize glucose.
These cells normally use a different chemical process called oxidative phosphorylation to obtain energy from glucose. With norepinephrine the cells no longer needed that process and could use metabolize glucose directly, in a process called glycolysis, a process used by cancer cells.
To confirm that the norepinephrine was causing this change, they deleted the gene in their animal model that produced the receptor nerepinephrine binds to on cells lining blood vessel walls. They found that those cells lacking the receptor then reverted to oxidative phosphorylation, which retrains formation of new blood vessels.
Coincidently, a class of drugs already approved for reducing blood pressure, called beta blockers, work by blocking the effects of norepinephrine and other chemicals. In addition, population studies in the past have shown that men with prostate cancer who took beta-blockers were linked with reduced metastasis and increased survival.
“Here we show that nerves stimulate the new blood vessels that encourage prostate tumor growth—and that we can short-circuit nerve stimulation to prevent new vessels from forming," Dr. Frenette said in a press release. "This opens up an entirely new strategy for treating prostate cancer—one that we may be able to pursue using existing drugs.”
The researchers are currently planning a pilot study in men with prostate cancer aimed at testing whether beta blockers can slow or reverse tumor growth.
Coincidently, a class of drugs already approved for reducing blood pressure, called beta blockers, work by blocking the effects of norepinephrine and other chemicals. In addition, population studies in the past have shown that men with prostate cancer who took beta-blockers were linked with reduced metastasis and increased survival.
“Here we show that nerves stimulate the new blood vessels that encourage prostate tumor growth—and that we can short-circuit nerve stimulation to prevent new vessels from forming," Dr. Frenette said in a press release. "This opens up an entirely new strategy for treating prostate cancer—one that we may be able to pursue using existing drugs.”
The researchers are currently planning a pilot study in men with prostate cancer aimed at testing whether beta blockers can slow or reverse tumor growth.
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