Granulocyte colony stimulating factor alters the phenotype of neuroblastoma cells: implications for disease-free survival of high-risk patients.
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.
Gay
Andre N
AN
Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030-2399, USA.
Chang
Shirong
S
Rutland
Lindsey
L
Yu
Ling
L
Byeseda
Sarah
S
Naik-Mathuria
Bindi
B
Cass
Darrell L
DL
Russell
Heidi
H
Olutoye
Oluyinka O
OO
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*
D004273:DNA, Neoplasm; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor