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

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. What's New? Granulocyte Colony Stimulating Factor (G-CSF) is known to mobilize hematopoietic progenitor stem cells in the blood of donors for stem cell transplantations, but its role as a neurotrophic factor is much less well understood. Here the authors show that G-CSF potentiates tumor growth and metastasis through autonomic nerve development in prostate tumors. This raises concerns regarding the use of G-CSF in cancer patients and gives insight into the interplay between tumor nerve development and growth factors as a potential new target in cancer therapy.