In some patients with solid tumors — for instance, those of the pancreas, head and neck, or prostate — cancerous cells can invade nerves surrounding the tumor, track along the nerves, and ultimately extend to the brain or spinal cord. Nerve invasion can lead to pain and paralysis, and make cancer more difficult to eradicate. It is also associated with a poorer prognosis.
Now a recent study led by Memorial Sloan-Kettering surgeons Richard J. Wong, Yuman Fong, and Jatin P. Shah has uncovered a mechanism that allows tumor cells to sense the presence of a nerve and migrate along it. Their findings were reported in January in the Journal of the National Cancer Institute. [PubMed Abstract]
The investigators used human cancer cell lines and grew the cells in a petri dish alongside nerve tissue. “Some cancer cells had a tendency to migrate toward nerve fibers and crawl along them, as if something around the nerves was attracting them,” explained Dr. Wong.
He and his colleagues found that a protein called GDNF, which is secreted by some nerve cells, guides the migration of tumor cells. In experiments in mice, the investigators were able to prevent pancreatic cancer cells from invading nerves by administering a compound that makes the cells unable to respond to GDNF by blocking its receptor.
Dr. Wong and colleagues are now investigating whether similar mechanisms are at work in patients with tumors that invade nerves. “There is already evidence that our findings are applicable in patients,” he said. “Future work might allow us to predict if a cancer will have neural invasive behavior. New therapies might also be developed to prevent neural invasion from happening while a patient is undergoing cancer treatment, with the ultimate goal of preserving nerve function and reducing pain.”