Tumour-induced neoneurogenesis and perineural tumour growth: a mathematical approach

Sci Rep. 2016 Feb 10:6:20684. doi: 10.1038/srep20684.


It is well-known that tumours induce the formation of a lymphatic and a blood vasculature around themselves. A similar but far less studied process occurs in relation to the nervous system and is referred to as neoneurogenesis. The relationship between tumour progression and the nervous system is still poorly understood and is likely to involve a multitude of factors. It is therefore relevant to study tumour-nerve interactions through mathematical modelling: this may reveal the most significant factors of the plethora of interacting elements regulating neoneurogenesis. The present work is a first attempt to model the neurobiological aspect of cancer development through a system of differential equations. The model confirms the experimental observations that a tumour is able to promote nerve formation/elongation around itself, and that high levels of nerve growth factor and axon guidance molecules are recorded in the presence of a tumour. Our results also reflect the observation that high stress levels (represented by higher norepinephrine release by sympathetic nerves) contribute to tumour development and spread, indicating a mutually beneficial relationship between tumour cells and neurons. The model predictions suggest novel therapeutic strategies, aimed at blocking the stress effects on tumour growth and dissemination.

MeSH terms

  • Algorithms
  • Autonomic Nervous System / metabolism
  • Humans
  • Models, Biological*
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Nerve Growth Factors / metabolism
  • Neurons / metabolism
  • Receptors, Cholinergic / chemistry
  • Receptors, Cholinergic / metabolism


  • Nerve Growth Factors
  • Receptors, Cholinergic