Study Shows How Nerves Drive Prostate Cancer

Source: Albert Einstein College of Medicine

Summary: A new study reported that certain nerves support prostate cancer growth by initiating a switch responsible for proliferation tumor vessels.

After skin cancer, prostate cancer is the second most common cancer in men. According to the estimates of National Cancer Institute, 161,360 new cases of prostate cancer will be diagnosed in 2017 and 26,730 men will die from the disease which accounts for 4.4% of all cancer deaths. Researchers at Albert Einstein College of Medicine found that certain nerves help prostate cancer growth and its spread. More specifically, then nerves of sympathetic nervous system promote the growth of a tumor by producing norepinephrine (flight or fight hormone), which binds to the receptors on tumor connective-tissue cells and encourages tumor growth. The findings were published in the journal Science.

Prostate tumor growth

Tissue from an early-stage tumor developing in a mouse model of prostate cancer. Sympathetic-nerve fibers (green) are closely intertwined with blood vessels (white). Norepinephrine released by nerve fibers stimulates vessel proliferation that fuels tumor growth. Credit: Albert Einstein College of Medicine

In the current study, a mouse model of prostate cancer is used to know how nerves in connective tissue drive tumor growth. Nerve fibres release norepinephrine which binds to the receptors of endothelial cells of the inner lining of blood vessels. This binding triggers an angio-metabolic switch” which in turn changes how cells metabolize glucose. Generally, endothelial cells use oxidative phosphorylation to obtain energy from glucose but were now almost depending on glycolysis exclusively. Using glycolysis for metabolizing glucose is a phenomenon that had previously observed in cancer cells. To confirm norepinephrine’s role researchers deleted a gene in the mice that codes for norepinephrine’s receptor thereby norepinephrine’s binding target. Finally observation was endothelial cells were using oxidative phosphorylation instead of glycolysis and as a result, new vessels formation was inhibited. 

Prof. Paul Frenette said, “Solid tumors depend on an expanding blood supply to thrive”, “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. This opens up an entirely new strategy for treating prostate cancer—one that we may be able to pursue using existing drugs.”

“While we need to learn more about the role that norepinephrine-releasing nerves play in prostate cancer, it’s certainly worth exploring whether beta-blockers can improve disease outcomes.”

More Information: A.H. Zahalka et al. “Adrenergic nerves activate an angio-metabolic switch in prostate cancer”, Science (2017). … 1126/science.aah5072

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