title: Granulocyte colony stimulating factor alters the phenotype of neuroblastoma cells: implications for disease-free survival of high-risk patients.
abstract: BACKGROUND
  Granulocyte colony stimulating factor (GCSF) is commonly used for the treatment of chemotherapy-induced neutropenia. Despite high-dose intensive chemotherapy for advanced-stage neuroblastoma, the survival rate remains poor. Granulocyte colony stimulating factor therapy is quite common in these children; thus, we questioned its effect on neuroblastoma cells. We hypothesized that exogenous GCSF stimulates the proliferation and invasive character of neuroblastoma cells.
  
  
  METHODS
  Expression of a GCSF receptor in 5 different neuroblastoma cell lines was determined by polymerase chain reaction. In addition, we determined the effect of increasing doses of GCSF (0, 1 ng/mL, 10 ng/mL, 1 microg/mL, and 10 microg/mL) on DNA synthesis (BrdU assay), invasiveness (Matrigel invasion chambers), and cell proliferation.
  
  
  RESULTS
  We tested 5 neuroblastoma cell lines; all expressed the GCSF receptor. Granulocyte colony stimulating factor treatment resulted in significantly increased proliferation of SK-N-SH, SK-N-AS, and SHSY-5Y cells. Likewise, increased invasiveness of SK-N-SH cells was observed with GCSF treatment.
  
  
  CONCLUSIONS
  Our results indicate that neuroblastoma cell lines express the GCSF receptor and respond to exogenous GCSF by increased proliferation and invasiveness. These findings suggest that GCSF may stimulate the growth of neuroblastoma cells in patients undergoing high-dose chemotherapy with GCSF rescue and could have a significant impact on the ability to eradicate these tumors.
authors.affiliation: Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030-2399, USA.
authors.forename: Andre N
authors.initials: AN
authors.lastname: Gay
authors.forename: Shirong
authors.initials: S
authors.lastname: Chang
authors.forename: Lindsey
authors.initials: L
authors.lastname: Rutland
authors.forename: Ling
authors.initials: L
authors.lastname: Yu
authors.forename: Sarah
authors.initials: S
authors.lastname: Byeseda
authors.forename: Bindi
authors.initials: B
authors.lastname: Naik-Mathuria
authors.forename: Darrell L
authors.initials: DL
authors.lastname: Cass
authors.forename: Heidi
authors.initials: H
authors.lastname: Russell
authors.forename: Oluyinka O
authors.initials: OO
authors.lastname: Olutoye
mesh_terms: D020029:Base Pairing; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000096:biosynthesis; D018572:Disease-Free Survival; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007223:Infant; D009361:Neoplasm Invasiveness / Q000473:pathology* / Q000503:physiopathology*; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004273:DNA, Neoplasm; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor