Validity of HB-EGF as Target for Human Neuroblastoma Therapy

Anticancer Res. 2015 Aug;35(8):4433-40.


Background/aim: Neuroblastoma (NB) is the most common and lethal extracranial solid tumor in children. The present study aimed to verify that the heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a rational target in NB therapy.

Material and methods: We examined expression of EGFR ligands in four NB cell lines using 2-dimensional culture (DC) and 3DC conditions. To assess the anti-tumor effect of cross-reacting material 197 (CRM197), which is a specific inhibitor of HB-EGF, on NB cells, we also performed terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay to detect apoptotic cells.

Results: HB-EGF was predominantly expressed in two out of four NB cell lines under 2DC and 3DC conditions. CRM197 significantly induced apoptosis of NB cells with high HB-EGF expression.

Conclusion: HB-EGF plays an important role in neuroblastoma tumorigenesis and CRM197 showed an effective antitumor effect in neuroblastoma cells.

Keywords: CRM197; HB-EGF; Neuroblastoma.

MeSH terms

  • Apoptosis / drug effects*
  • Bacterial Proteins / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • ErbB Receptors / biosynthesis
  • Heparin-binding EGF-like Growth Factor / metabolism*
  • Humans
  • In Situ Nick-End Labeling
  • Molecular Targeted Therapy*
  • Neuroblastoma / drug therapy*


  • Bacterial Proteins
  • Heparin-binding EGF-like Growth Factor
  • CRM197 (non-toxic variant of diphtheria toxin)
  • EGFR protein, human
  • ErbB Receptors