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The nerve and prostate cancer - a symbiotic relationship

By Ruth SoRelle, MPH

Gustavo Ayala, MD

It's no secret that prostate cancer wraps around nerves. The process was first identified 100 years ago. What it means, though, could have important implications in the treatment of spreading prostate cancer in coming years.

Now Gustavo Ayala, MD, associate professor of pathology and his colleagues at Baylor College of Medicine in Houston are well on the road to finding out why this phenomenon occurs, what it means to patients and determining how to block it.

Perhaps it began when Thomas Wheeler, MD, BCM professor of pathology determined that the amount of tumor encasing the nerve in prostate cancer was in direct proportion to its virulence. In other words, the more cancer wrapped around the nerve, the worse the prognosis for the patient.

"It really is a very important predictor," said Ayala. "Not only for prostate cancer, but it also works for pancreatic cancer and cancers of the head and neck. These are neurotrophic cancers. They like to invade the nervous system."

Building on that in the laboratory, Ayala established a laboratory model of prostate cancer invading the nerves. What he found was surprising.

"The tumor grew more in the presence of the nerve, and the nerve grew more in the presence of the cancer," he said.

"The big question is 'why does this happen?'" he said. The answer lies in the biological programming of the cells. Like humans, all cells must die. They are programmed to die in a certain space of time - a process called programmed cell death or apoptosis. Life is short for the cells in the skin, which slough off daily. Nerve cells are a different story. They are programmed to live as long as the organism itself.

"The nerve cells have to shut down the mechanisms of apoptosis," said Ayala. "When the cancer starts wrapping around the nerve, it begins feeding off the mechanisms the nerve uses to avoid death. The cancer becomes a parasite of the nerve."

This enables the cancer to shut down its own apoptotic mechanisms and to reproduce prolifically.

Using a special technique called a cDNA array, he found 15 genes that were upregulated (especially active) in this activity. One he has studied is called nuclear factor Kappa B. When this gene goes to the nucleus, it becomes a transcription factor - a component of the mechanism that translates the genetic information in a gene into a protein.

In studies of tissues from 250 patients with prostate cancer, Ayala and his colleagues have found that when  nuclear factor Kappa B acts strongly in the nucleus of the cells, the patient is more likely to have the prostate cancer return and return sooner. He and his colleagues analyzed only the cancer directly around the nerve.

"That's significant," said Ayala. "Only when the gene goes to nucleus do you have a worse prognosis."

The next question was how does the cancer get around the nerve? Ayala said he has a candidate gene that may answer that question. The normal function of the gene has nothing to do with the prostate, but tests are promising, he said.

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