Nerves Play Key Role in Triggering Prostate Cancer and Promoting Metastases
Researchers at Albert Einstein College of Medicine of Yeshiva University have found that nerves play a critical role in both the development and spread of prostate tumors. 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, led by Paul Frenette, MD, Professor of Medicine and of Cell Biology and Director of the Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research at Einstein, was published online today in Science.
In earlier research, Dr. Frenette and colleagues had discovered that the sympathetic nervous system regulates hematopoietic stem cell niches. Nerves are commonly found around tumors, but their role in the growth and progression of cancer has not been clear. "Since there might be similarities between the hematopoietic stem cell niche and the stem cell niches found in cancer, we thought that sympathetic nerves might also have a role in tumor development," said Dr. Frenette. "It turns out that in prostate cancer, not only are sympathetic nerves involved, but so too are parasympathetic nerves."
Branches of Nervous System Have Complementary Functions
The researchers 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 nervous system 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. The sympathetic nervous system promotes tumor growth by producing the neurotransmitter 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 parasympathetic nervous system's role in cancer progression, the researchers found that it promotes tumor metastases 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.
Higher Density of Nerves in Aggressive Prostate Cancers
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. "More work needs to be done, but the findings suggest that nerve density assessment merits further study as a possible predictive marker of prostate cancer aggressiveness," said Dr. Frenette.
Whether these findings apply to other forms of cancer is uncertain. "Clinical studies show that breast cancer patients who took beta-blockers did better than those who were not taking beta-blockers," said Dr. Frenette. "This suggests that the same mechanisms are involved, but that remains to be seen."
The study was supported by an Idea Development award from the Department of Defense (W81XWH-07-1-0165) and grants from the National Institutes of Health. 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.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
