Researchers have found parallels between tissue regeneration, nerve growth and tumour development, confirming that the nervous system is actively involved in triggering cancer.

A group led by University of Newcastle biochemistry researcher Hubert Hondermarck has found parallels between tissue regeneration, nerve growth and tumour development, confirming for the first time that the nervous system is strongly implicated in the onset and spread of cancer.

While tumour cells were known to invade nerves, Professor Hondermarck says it was thought that the nerves themselves weren’t involved in initiation and progression of cancer.

“We and other teams in the world have found there is a direct cross-talk between nerves and cancer cells,” Professor Hondermarck says. “And the more nerves there are, the more aggressive a tumour is.

“It’s not entirely clear why, but we know that nerves release stimulatory molecules such as neurotransmitters. Cancer cells receive these and use them for their benefit, growing, multiplying, migrating, invading and creating metastasis – there is therefore a nerve dependence for cancer cells.

“At the same time, cancer cells secrete neurotrophic growth factors, which are molecules that stimulate the outgrowth of nerves in the tumours. This may be a trigger point where the tumours stimulate their own innervation and growth.”

The phenomenon has been demonstrated by several teams, including Professor Hondermarck’s, in prostate, gastric, breast and pancreatic tumours, leading the research team to suspect it is relatively widespread. Given the nerve dependence, they believe it relates to the body’s regeneration process going awry.

Professor Hondermarck collaborated with UON neurophysiologist Dr Phil Jobling, who was able to identify the presence of nerve fibres as tiny as 1μm (micrometre) where conventional histology would miss them. Professors Marjorie Walker, Jim Denham and John Forbes, along with PhD student Sam Faulkner, were also involved.

The study has just been published in the premier international cancer journal Cancer Cell*. Next challenge is to translate the laboratory finding into clinical practice.

“In preclinical models we looked at targeting neurotrophic growth factors to deprive the tumor from nerve infiltration,” Professor Hondermarck adds. “In the future, anti-cancer drugs could potentially block the stimulatory impact of nerves.”

There is also potential to develop diagnostic and prognostic tools for cancer, either by determining tumour aggressiveness through the presence of nerves, or using neurotrophic growth factors as a blood biomarker to signify a cancer is starting to develop.

Knowing there is a crosstalk between the nervous system and cancer cells, Professor Hondermarck says it is now possible to imagine potential brain-cancer interactions.

“It at least raises a larger question, which is the possibility of a higher-order control of cancer growth and regeneration with sensory input. I think it shows the importance of broadening the perspective of cancer research to incorporate ideas from development, regeneration, stem cells and neuroscience.”

Professor Hondermarck is a member of the HMRI Cancer Research Program. The study was supported by the University of Newcastle, Hunter Medical Research Institute, Hunter Cancer Research Alliance and Hunter New England Local Health District. HMRI is a partnership between the University of Newcastle, Hunter New England Health and the community.

* Boilly B, Faulkner S, Jobling P, Hondermarck H. Nerve Dependence: From Regeneration to Cancer. Cancer Cell. 2017 Mar 13;31(3):342-354. doi: 10.1016/j.ccell.2017.02.005.