One Nervous Tumor: Nerve Cells Promote Spread Of Prostate Cancer, Beta Blockers Offer Possible Route For Therapy
The brain controls everything from our emotions to our movements... but what if it also regulated our cancers? New research shows that nerves cells play a critical role in the establishment and spread of prostate cancer. Furthermore the study, which was published today in Science, suggests that drugs that target nerve cells could provide a way for treating the deadly disease.
Prostate cancer is the second most common cancer in men behind skin cancer. However, it is far more devastating, with nearly 30,000 Americans and over a quarter million men worldwide patients slated to succumb to the disease this year.
A major barrier to treating the disease is metastasis, or migrating of cancer cells from their initial site within the prostate. There is currently no way to treat the disease once this occurs.
Scientists at the Albert Einstien College of Medicine suspected that nerve cells, which carry signal from the brain to the prostate, might be involved with cancer spread. Tumor cells are known to usurp the microenvironment of the body's healthy tissue, plus prior work had observed a higher density of nerve fibers around prostate cancers.
Nerves that lead to the prostate fall into two distinct branches: the sympathetic and parasympathetic nervous system. These two systems play contrasting roles in our "fight-or-flight" response.
Can I check your prostate, Mr. Mouse?
Using nerve-blocking drugs and genetic modification, the scientists were able to show that each branch plays a specific role in prostate cancer in mouse models of the disease.
The sympathetic system was involved in the early stages of cancer development, with tumors having a harder time with growing without these nerve cells.
In contrast, the parasympathetic neurons played a bigger role with metastasis in two different ways. Blocking this variety of nerves prevented tumor cells from leaving the prostate and impaired their ability to invade other organs. The doctors tracked the spread of tumor cells with bioluminescent markers as well as positron emission tomography (PET) scanners.
"It turns out that in prostate cancer, not only are sympathetic nerves involved, but so too are parasympathetic nerves," said lead author Dr. Paul Frenette, a stem cell expert at Einstein. In prior work, Frenette had discovered that the sympathetic nervous system governs stem cell function in the bone marrow. This gave him the initial idea to look at the connection between nerve cell and cancer, given tumor cells can sometimes behave like stem cells.
The researchers followed up their mouse experiments with an investigation in human prostate cancer patients. They found that patients with more aggressive tumors had a higher density of nerve fibers than patients with 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 Frenette.
The results provide a possible explanation for why prostate cancer patients who take beta-blockers, which are drugs that inhibit sympathetic nerves, tend to survive more than those not taking the drugs. At the same time, the researchers are excited by the idea of exploring how drugs that target parasympathetic nerves impact prostate cancer patients, which has not been investigated in the past.
"[Our results are] consistent with recent epidemiological studies showing that the use of beta-blockers, which lower blood pressure by blocking beta-adrenergic receptors [in sympathetic neurons], is associated with improved survival of prostate cancer patients," said Frenette.
And prostate tumors may not be the type of cancer that could benefit from this putative strategy.
"Our findings raise the tantalizing possibility that drugs targeting both branches of the autonomic nervous system may be useful therapies for prostate cancer," Frenette added. "Clinical studies show that breast cancer patients who took beta blockers did better than those who were not taking beta blockers. This suggests that the same mechanisms are involved, but that remains to be seen."
Source: Magnon C, Hall SJ, Lin J, et al. Autonomic Nerve Development Contributes to Prostate Cancer Progression. Science. 2013.