Neuroepithelial Interactions in Cancer.

Nerves not only regulate the homeostasis and energetic metabolism of normal epithelial cells but also are critical for cancer, as cancer recapitulates the biology of neural regulation of epithelial tissues. Cancer cells rarely develop in denervated organs, and denervation affects tumorigenesis, in vivo and in humans. Axonogenesis occurs to supply the new malignant epithelial growth with nerves. Neurogenesis happens later, first in ganglia around organs or the spinal column and subsequently through recruitment of neuroblasts from the central nervous system. The hallmark of this stage is regulation of homeostasis and energetic metabolism. Perineural invasion is the most efficient interaction between cancer cells and nerves. The hallmark of this stage is increased proliferation and decreased apoptosis. Finally, carcinoma cells transdifferentiate into a neuronal profile in search of neural independence. The latter is the last stage in neuroepithelial interactions. Treatments for cancer must address the biology of neural regulation of cancer.