Induced differentiation inhibits sphere formation in neuroblastoma

Brian T. Craig, Eric J. Rellinger, Alexandra L. Alvarez, Haley L. Dusek, Jingbo Qiao, Dai H. Chung

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Neuroblastoma arises from the neural crest, the precursor cells of the sympathoadrenal axis, and differentiation status is a key prognostic factor used for clinical risk group stratification and treatment strategies. Neuroblastoma tumor-initiating cells have been successfully isolated from patient tumor samples and bone marrow using sphere culture, which is well established to promote growth of neural crest stem cells. However, accurate quantification of sphere-forming frequency of commonly used neuroblastoma cell lines has not been reported. Here, we show that MYCN-amplified neuroblastoma cell lines form spheres more frequently than non-MYCN-amplified cell lines. We also show that sphere formation is directly sensitive to cellular differentiation status. 13-cis-retinoic acid is a clinically used differentiating agent that induces a neuronal phenotype in neuroblastoma cells. Induced differentiation nearly completely blocked sphere formation. Furthermore, sphere formation was specifically FGF-responsive and did not respond to increasing doses of EGF. Taken together, these data suggest that sphere formation is an accurate method of quantifying the stemness phenotype in neuroblastoma.

Original languageEnglish
Pages (from-to)255-259
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number2
StatePublished - Aug 19 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Inc.


  • Cancer stem cell
  • Limiting dilution analysis
  • Neuroblastoma
  • Retinoic acid
  • Sphere assay

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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