title: Validity of HB-EGF as Target for Human Neuroblastoma Therapy.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  HB-EGF plays an important role in neuroblastoma tumorigenesis and CRM197 showed an effective antitumor effect in neuroblastoma cells.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan Central Research Institute for Advanced Molecular Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Sung Ouk
authors.initials: SO
authors.lastname: Nam
authors.affiliation: Central Research Institute for Advanced Molecular Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan Department of Biochemistry, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Fusanori
authors.initials: F
authors.lastname: Yotsumoto
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan Central Research Institute for Advanced Molecular Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Miyata
authors.affiliation: Department of Pediatric Surgery, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Souzaki
authors.affiliation: Department of Pediatric Surgery, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Taguchi
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Kuroki
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan Central Research Institute for Advanced Molecular Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan smiya@cis.fukuoka-u.ac.jp.
authors.forename: Shingo
authors.initials: S
authors.lastname: Miyamoto
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001426:Bacterial Proteins / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000096:biosynthesis; D066257:Heparin-binding EGF-like Growth Factor / Q000378:metabolism*; D006801:Humans; D020287:In Situ Nick-End Labeling; D058990:Molecular Targeted Therapy; D009447:Neuroblastoma / Q000188:drug therapy*
chemical_list: D001426:Bacterial Proteins; D066257:Heparin-binding EGF-like Growth Factor; C028581:CRM197 (non-toxic variant of diphtheria toxin); C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: CRM197; HB-EGF; Neuroblastoma