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Biological Chemistry

Nerve signaling encourages tumor growth

Neurotransmitters act through adrenergic receptors to promote formation of tumor blood vessels

by Michael Torrice
October 30, 2017 | APPEARED IN VOLUME 95, ISSUE 43

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Credit: Science
Noradrenaline released by nerve cells promotes angiogenesis by activating ADRβ2 on blood vessel endothelial cells, which in turn ensures the cells metabolize glucose through glycolysis.
Credit: Science
Noradrenaline released by nerve cells promotes angiogenesis by activating ADRβ2 on blood vessel endothelial cells, which in turn ensures the cells metabolize glucose through glycolysis.

Nerves inside prostate tumors release chemical compounds that stimulate the growth of blood vessels feeding the cancer cells, according to a study in mice (Science 2017, DOI: 10.1126/science.aah5072). Therapies that block this type of chemical signaling could help slow the growth of tumors, the researchers say. In 2013, Paul S. Frenette of Albert Einstein College of Medicine and colleagues found that destroying nerves in tumors halted the progression of prostate cancer in mice. These specific nerves send signals by releasing the neurotransmitter noradrenaline, which binds to the β2-adrenergic receptor (ADRβ2). In the new study, the researchers determined that noradrenaline activates ADRβ2 in the endothelial cells of the mice’s blood vessels. Once activated, ADRβ2 promotes the formation of new blood vessels—a process called angiogenesis—by ensuring the cells continue to metabolize glucose through glycolysis. When the researchers knocked out the gene for ADRβ2 in the endothelial cells, the cells used an alternative metabolic pathway called oxidative phosphorylation, and as a result, there was little blood vessel growth. Frenette points out that some anticancer therapies targeting angiogenesis have not had long-term success against prostate tumors. He proposes studying the effectiveness of targeting angiogenesis along with nerve signaling with β-blockers, which inhibit ADRβ2.

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