Progenitors from the central nervous system drive neurogenesis in cancer

Nature. 2019 May;569(7758):672-678. doi: 10.1038/s41586-019-1219-y. Epub 2019 May 15.

Abstract

Autonomic nerve fibres in the tumour microenvironment regulate cancer initiation and dissemination, but how nerves emerge in tumours is currently unknown. Here we show that neural progenitors from the central nervous system that express doublecortin (DCX+) infiltrate prostate tumours and metastases, in which they initiate neurogenesis. In mouse models of prostate cancer, oscillations of DCX+ neural progenitors in the subventricular zone-a neurogenic area of the central nervous system-are associated with disruption of the blood-brain barrier, and with the egress of DCX+ cells into the circulation. These cells then infiltrate and reside in the tumour, and can generate new adrenergic neurons. Selective genetic depletion of DCX+ cells inhibits the early phases of tumour development in our mouse models of prostate cancer, whereas transplantation of DCX+ neural progenitors promotes tumour growth and metastasis. In humans, the density of DCX+ neural progenitors is strongly associated with the aggressiveness and recurrence of prostate adenocarcinoma. These results reveal a unique crosstalk between the central nervous system and prostate tumours, and indicate neural targets for the treatment of cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / pathology
  • Adrenergic Neurons / pathology
  • Animals
  • Carcinogenesis
  • Cell Differentiation
  • Central Nervous System / pathology*
  • Disease Models, Animal
  • Genes, myc
  • Humans
  • Lateral Ventricles / pathology
  • Male
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / pathology*
  • Neurogenesis*
  • Neuropeptides / metabolism
  • Olfactory Bulb / pathology
  • Prognosis
  • Prostatic Neoplasms / pathology*

Substances

  • Microtubule-Associated Proteins
  • Neuropeptides
  • doublecortin protein