Granulocyte colony-stimulating factor off-target effect on nerve outgrowth promotes prostate cancer development

Int J Cancer. 2015 Feb 15;136(4):982-8. doi: 10.1002/ijc.29046. Epub 2014 Jul 9.

Abstract

The hematopoietic growth factor granulocyte colony-stimulating factor (G-CSF) has a role in proliferation, differentiation and migration of the myeloid lineage and in mobilizing hematopoietic stem and progenitor cells into the bloodstream. However, G-CSF has been newly characterized as a neurotrophic factor in the brain. We recently uncovered that autonomic nerve development in the tumor microenvironment participates actively in prostate tumorigenesis and metastasis. Here, we found that G-CSF constrains cancer to grow and progress by, respectively, supporting the survival of sympathetic nerve fibers in 6-hydroxydopamine-sympathectomized mice and also, promoting the aberrant outgrowth of parasympathetic nerves in transgenic or xenogeneic prostate tumor models. This provides insight into how neurotrophic growth factors may control tumor neurogenesis and may lead to new antineurogenic therapies for prostate cancer.

Keywords: G-CSF; autonomic nervous system; hematopoietic cytokine; tumor microenvironment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adrenergic Fibers / pathology
  • Adrenergic Fibers / physiology
  • Animals
  • Axons / pathology
  • Axons / physiology*
  • Carcinogenesis / metabolism*
  • Cell Survival
  • Granulocyte Colony-Stimulating Factor / physiology*
  • HL-60 Cells
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Nude
  • Neoplasm Transplantation
  • Nerve Growth Factors / physiology
  • Prostate / innervation
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology

Substances

  • Nerve Growth Factors
  • Granulocyte Colony-Stimulating Factor