Norepinephrine may increase blood vessel growth in prostate cancer tumors.
Certain nerves may promote prostate cancer growth by provoking blood vessel proliferation, according to a new study published by Science. The study results also suggest that beta blockers may be able to kill prostate cancer cells.
“Solid tumors depend on an expanding blood supply to thrive,” said lead researcher Paul Frenette, MD. “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.”
Prostate cancer is the second most common cancer in men, with more than 161,000 new cases diagnosed in 2017. Understanding what fuels cancer progression can lead to better treatments and optimal patient outcomes, according to the study authors.
The team of researchers previously found that nerve cells played a crucial role in prostate cancer. Specifically, nerves in the sympathetic nervous system were observed to create norepinephrine, which binds to and stimulates receptors on cancer connective tissue cells, according to the authors.
In the current study, the authors examined how nerves in connective tissue can result in prostate cancer growth in mice models.
After norepinephrine is released by nerve fibers, it binds to receptors on endothelial cells that line blood vessels. The authors discovered that this action hits an angio-metabolic switch, which alters how glucose is metabolized, according to the study.
Instead of using oxidative phosphorylation, endothelial cells were primarily relying on glycolysis to gain energy from glucose, according to the authors. Using glycolysis for glucose metabolism has previously been linked to cancer cells.
To determine how norepinephrine is involved with the metabolic switch, the investigators deleted a gene that codes for the receptor on blood vessel cells to remove the binding target, according to the study.
A lack of this binding site resulted in cells reverting back to oxidative phosphorylation and blocked new blood vessel creation.
“Oxidative phosphorylation generates more energy than glycolysis,” Dr Frenette said. “It may seem counter-intuitive, but this energy boost provided by oxidative phosphorylation diminishes endothelial cell function and inhibits angiogenesis—the formation of new blood vessels that sustains tumor growth.”
In the mouse model, the investigators found that stimulation from norepinephrine resulted in endothelial cells using glycolysis, leading to disease progression from a precancerous state to high-grade malignant state, according to the study.
The authors hypothesize that beta blockers could be used to inhibit the effects of norepinephrine and related compounds in prostate cancer. Other studies have suggested that these drugs may reduce metastasis and increase survival among men with prostate cancer.
“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,” Dr Frenette said.