Nerves play role in triggering prostate Ca, mets

Nerves play a critical role in both the development and spread of prostate tumors, report researchers at Albert Einstein College of Medicine of Yeshiva University, Bronx, NY.

Study authors say their findings, using both a mouse model and human prostate tissue, may lead to new ways to predict the aggressiveness of prostate cancer and to novel therapies for preventing and treating the disease. The study was published online last week in Science (July 12, 2013).

In earlier research, Paul Frenette, MD, and colleagues had discovered that the sympathetic nervous system regulates hematopoeitic stem cell niches-the sites in bone marrow where red blood cells are formed. Dr. Frenette is the lead author of the current study.

"Since there might be similarities between the hematopoeitic stem cell niche and the stem cell niches found in cancer, we thought that sympathetic nerves might also have a role in tumor development," Dr. Frenette said. "It turns out that in prostate cancer, not only are sympathetic nerves involved, but so too are parasympathetic nerves."

Dr. Frenette’s team discovered the role of nerves in prostate cancer by first injecting human prostate cancer cells into mice and then systematically disabling various parts of the sympathetic and parasympathetic nervous system and observing how the cells fared. A control group of mice were administered the cancer cells but underwent no further interventions.

The study found that the autonomic nervous system's two branches have complementary functions in the development and spread of prostate cancer. More specifically, the researchers found that the SNS promotes tumor growth by producing norepinephrine, which then binds to and stimulates two types of adrenergic receptors (beta-2 and beta-3) on the surface of the stromal cells in the tumor.

"This is consistent with recent epidemiological studies showing that the use of beta-blockers, which lower blood pressure by blocking beta-adrenergic receptors, is associated with improved survival of prostate cancer patients," said Dr. Frenette.

As for the PNS's role in cancer progression, it makes tumor cells invade other tissues and metastasize when its nerve fibers release acetylcholine, which activates a signaling pathway in stromal cells of the tumor microenvironment.

"Our findings raise the tantalizing possibility that drugs targeting both branches of the autonomic nervous system may be useful therapies for prostate cancer," Dr. Frenette added.

To see whether their findings were relevant to human cancer, the researchers analyzed nerve fiber densities in prostate tissue specimens taken from 43 patients with prostate cancer who had not undergone any treatment. Patients who turned out to have aggressive prostate cancers had a higher density of nerve fibers within tumors and in normal prostate tissue surrounding their tumors compared with patients who had less aggressive tumors.

Albert Einstein College of Medicine has a pending U.S. patent application relating to the use of adrenergic and muscarinic receptors antagonists for cancer therapy, which is currently available for licensing.

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