Nerves spawned by prostate cancer

By Ruth SoRelle, M.P.H.

Gustavo Ayala, M.D.

Just as cancer promotes the growth of new blood vessels to nurture its insidious spread, prostate cancer spawns new nerves and the branching axons that carry their messages, said researchers from Baylor College of Medicine in the first report of the phenomenon that appears today in the journal Clinical Cancer Research.

The prostate cancers associated with new nerve growth are more aggressive, an important finding, said Gustavo Ayala, M.D., professor of pathology and urology at BCM. This is the first report demonstrating that tumors actually promote nerve growth. Ayala thinks this phenomenon may occur in other tumors as well as those of the prostate.

First report

"This is the first report of this phenomenon," said Ayala. "It represents an important new target in prostate cancer treatment, as prostate cancers are more aggressive when neurogenesis is present."

Ayala noted that this finding is comparable to the discovery of angiogenesis or the growth of new blood vessels. Both are part of the wound repair process.

"We also believe that axongenesis and neurogenesis are found not only in prostate cancer, but is potentially a more global phenomenon, particularly relating to those cancers that grow along nerve paths," said Ayala, also a researcher in the Dan L. Duncan Cancer Center at BCM.

Neurogenesis on many fronts

Ayala and his colleagues studied the neurogenesis in tissue culture, in human tissues of patients who had prostate cancer and compared to prostate tissues from patients who had died of other ailments. They calculated the density of nerves in human prostate tissues, including those with prostate cancer. They found that nerve density was considerably higher in patients with prostate cancer and in precancerous lesions. As part of the study, Ayala and colleagues used an entire prostate gland to reconstruct the prostate and enable scientists to see the growth of nerves and axons in three-dimensions, a computerized process that took substantial continuous computer processing.

Protein regulator

He and his colleagues have even identified a possible method of regulating the growth of new nerves and axons through a protein called semaphorin 4F. Semaphorins are embryologically active molecules that regulate nerve growth and direction. Most disappear in adults, but semaphoring 4F is active in wound repair. When prostate cancer cells overproduce semaphorin 4F, new nerves result. Blocking semaphoring 4F prevents the growth of new nerves.

Others who took part in this research include: Hong Dai, Michael Powell, Rile Li, Yi Ding, Thomas M. Wheeler, David Shine, Timothy Thompson, Dov Kadmon, Brian J. Miles, Michael M. Ittmann and David Rowley, all of BCM. Thompson is now with The University of Texas M.D. Anderson Cancer Center.

Funding for this research came from the National Institutes of Health and the Tumor Microenvironment Network of the National Cancer Institute.

The full article is available at http://clincancerres.aacrjournals.org