Nerve growth triggers prostate cancer

New research suggests that the formation of new nerve fibers in and around prostate tumors increases cancer growth and spreading.

With more than 58,000 new cases every year, prostate cancer is the most common type of cancer affecting German men. Although prostate cancer survival expectations are highly favorable, with over 80% of patients surviving for over 10 years after diagnosis, it is estimated that the number of affected males each year may reach 80,000 by 2020.

Now, a research team led by Dr. Paul Frenette at the Albert Einstein College of Medicine, in the US, has shown that nerves can play a key role in the development and progression of prostate tumors in mice and human tumor tissue. The results open the way to potential new treatments and better methods to predict cancer aggressiveness.

Nerves are commonly found around and inside tumors, but their role in cancer progression has remained a mystery. It turns out that, at least in prostate cancer, the sympathetic and the parasympathetic nerves - the two branches of the nervous system that regulate automatic functions, like heart rate and digestion - are involved in cancer growth and spreading.

One of the main functions of the sympathetic nerve system (or SNS) is to control the body's responses to unexpected or stressful situations, by increasing heart rate or sweating, for instance. These physiological reactions are known as 'fight or flight' responses. The parasympathetic nerve system (or PNS), on the other hand, works in opposition to the SNS, by trying to keep the body in 'balance'. Both components rely on strong chemical signals, such as neurotransmitters, to convey their message.

In earlier research, Dr. Frenette's team established that signals from the SNS regulate migration of cells that give rise to the bone marrow, called hematopoeitic stem cells. From those results, Dr Frenette hypothesized that "there might be some similarities between healthy and cancer stem cells," he says. To test whether the nervous system impacts on tumor growth, the team used prostate cancer as a model "because the prostate is highly innervated," says Dr Frenette.

In their new research, which was reported in a July Science study, Dr Frenette's team first developed a way to assess tumor growth over time. They injected mice with fluorescent prostate human cancer cells and then checked the animals regularly as the cancer developed. After 11 weeks, prostate tumors were obvious in all animals tested and a network of sympathetic and parasympathetic nerves had formed inside and around the tumors.

But are these newly-formed nerve fibers important for cancer progression? To answer this question, the researchers shut down different parts of the SNS or PNS using specific drugs or surgical procedures. Blocking SNS activity prevented the formation of tumors; blocking the PNS didn't have such a dramatic effect, but it reduced the incidence of metastasis, or cancer spreading.

The researchers concluded that SNS fibers are relevant during the initial phases of cancer development, whereas PNS fibers stimulate cancer invasion of neighboring tissues and eventually metastasis. How exactly SNS and PNS signals promote cancer growth and spreading is still unknown, explains Dr Frenette, but there is some evidence to suggest that certain neurotransmitters released by the SNS or PNS can stimulate cell survival and migration.

To determine whether these results are relevant to humans, the team quantified the number of nerve fibers in tissue samples taken from 43 men diagnosed with prostate cancer, but who had not undergone any treatment. Patients with more nerve fibers in and around the tumors had more aggressive types of cancer than patients with less innervated tumors. This assessment of fiber density in and around tumors certainly merits further research as a potential method to predict cancer aggressiveness.

"Although further studies will be required, our data raise the tantalizing possibility that drugs targeting both branches of the nervous system may be useful therapeutics for prostate cancer", says Dr Frenette. "We are currently planning the next step and I hope we can design a clinical trial, but we need to have the proper drugs and design."