Neuroblastoma as an experimental model for neuronal differentiation and hypoxia-induced tumor cell dedifferentiation

Semin Cancer Biol. 2007 Jun;17(3):248-56. doi: 10.1016/j.semcancer.2006.04.005. Epub 2006 May 10.


Neuroblastoma is a childhood tumor derived from precursor or immature cells of the sympathetic nervous system. Neuroblastomas show a tremendous clinical heterogeneity, encompassing truly benign as well as extremely aggressive forms. In vivo as well as in vitro data have shown that the degree of sympathetic neuronal tumor cell differentiation influences patient outcome. Unraveling mechanisms governing neuroblastoma cell differentiation is therefore a central issue in the neuroblastoma research field. In this communication, we discuss some of the in vitro models frequently used to study human neuroblastoma cell differentiation. We also review recent data demonstrating that oxygen shortage, hypoxia, shifts neuroblastoma cells toward an immature, stem cell-like phenotype and discuss the potential clinical impact of hypoxia on neuroblastoma behavior.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Differentiation / physiology*
  • Cell Hypoxia
  • Humans
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology*
  • Neurons / cytology*
  • Neurons / metabolism