Neoneurogenesis: tumors may initiate their own innervation by the release of neurotrophic factors in analogy to lymphangiogenesis and neoangiogenesis

Med Hypotheses. 2006;67(1):33-5. doi: 10.1016/j.mehy.2006.01.015. Epub 2006 Mar 3.

Abstract

Malignant tumors frequently release angiogenic factors, which lead to the vascularization of the tumor, a process called neoangiogenesis. This neoangiogenesis provides sufficient nourishment of the tumor when it exceeds a certain size. Recently, a similar mechanism has been postulated for the development of new lymph vessels in tumors, termed lymphangiogenesis. Thus, tumors get access to the circulation and lymph drainage like any other growing or regenerating tissue. Furthermore, it has been hypothesized that neoangiogenesis and lymphangiogenesis support metastasis development. Elaborating on this model, we herein present strong arguments for the new theory that tumors initiate their own innervation by the release of neurotrophic factors in analogy to lymphangiogenesis and neoangiogenesis. For this process, we coin the term neoneurogenesis. It is likely that neoneurogenesis further supports the formation of metastases, since the ingrown nerve endings can release neurotransmitters which enhance the metastasis development. Strikingly, the presence of nerve cell markers in tumor tissues has been shown to be a prognostic marker for the course of a cancer disease, and we have recently reported on the metastasis-increasing function of the neurotransmitter norepinephrine in a mouse model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Disease Progression
  • Humans
  • Lymph Nodes / pathology*
  • Mice
  • Neoplasm Metastasis
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Neovascularization, Pathologic*
  • Nerve Growth Factors / metabolism*
  • Neurons / pathology*
  • Neurotransmitter Agents
  • Norepinephrine / metabolism
  • Prognosis

Substances

  • Nerve Growth Factors
  • Neurotransmitter Agents
  • Norepinephrine