Korean J Hematol.  2012 Sep;47(3):219-224. 10.5045/kjh.2012.47.3.219.

Effects of granulocyte-colony stimulating factor and the expression of its receptor on various malignant cells

• Moon HW
• Kim TY
• Oh BR
• Hwang SM
• Kwon J
• Ku JL
• Lee DS

• KMID: 2251957
• DOI: http://doi.org/10.5045/kjh.2012.47.3.219

Abstract

BACKGROUND
Granulocyte-colony stimulating factor (G-CSF) is extensively used to improve neutrophil count during anti-cancer chemotherapy. We investigated the effects of G-CSF on several leukemic cell lines and screened for the expression of the G-CSF receptor (G-CSFR) in various malignant cells.
METHODS
We examined the effects of the most commonly used commercial forms of G-CSF (glycosylated lenograstim and nonglycosylated filgrastim) on various leukemic cell lines by flow cytometry. Moreover, we screened for the expression of G-CSFR mRNA in 38 solid tumor cell lines by using real-time PCR.
RESULTS
G-CSF stimulated proliferation (40-80% increase in proliferation in treated cells as compared to that in control cells) in 3 leukemic cell lines and induced differentiation of AML1/ETO+ leukemic cells. Among the 38 solid tumor cell lines, 5 cell lines (hepatoblastoma, 2 breast carcinoma, squamous cell carcinoma of the larynx, and melanoma cell lines) showed G-CSFR mRNA expression.
CONCLUSION
The results of the present study show that therapeutic G-CSF might stimulate the proliferation and differentiation of malignant cells with G-CSFR expression, suggesting that prescreening for G-CSFR expression in primary tumor cells may be necessary before using G-CSF for treatment.

Keyword

G-CSF; Differentiation; Proliferation; Solid tumor; AML

MeSH Terms

Breast
Carcinoma, Squamous Cell
Cell Line
Cell Line, Tumor
Flow Cytometry
Granulocyte Colony-Stimulating Factor
Larynx
Melanoma
Neutrophils
Receptors, Granulocyte Colony-Stimulating Factor
Recombinant Proteins
RNA, Messenger
Granulocyte Colony-Stimulating Factor
RNA, Messenger
Receptors, Granulocyte Colony-Stimulating Factor
Recombinant Proteins

Figure

• 

  Fig. 1 Expression of G-CSFR in hematologic malignancies and solid tumors using real-time PCR. Among hematologic malignancies, Kasumi-1 and K562 expressed G-CSFR mRNA whereas CTV-1 and U266 did not. Among 38 solid tumor cell lines, 5 cell lines (13.1%) expressed G-CSFR mRNA. The G-CSFR expression of each cell type was normalized to GAPDH expression. The relative expressions were presented as relative ratios compared to gene expression in Kasumi-1 cells (set to 1.0). Results shown are mean values from 3 experiments.

• 

  Fig. 2 Proliferation effects of lenograstim (left column) and filgrastim (right column) on Kasumi-1, CTV-1, K562, and U266 cells at different concentrations (10, 50, and 100 ng/mL) after 72 h-incubation. The relative proliferation was expressed as percentage of unstimulated control cells (set to 100%).

• 

  Fig. 3 Proliferation effects of lenograstim and filgrastim on Kasumi-1 cells according to incubation time at 10 ng/mL concentration of G-CSF. Both forms of G-CSF significantly stimulated the proliferation of AML1/ETO+ Kasumi-1 cells in a time-dependent manner.

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  Fig. 4 The differentiation effects of filgrastim (F) and lenograstim (L) on Kasumi-1 and CTV-1 cell lines and unstimulated control cells (C) after 14 d of incubation at 100 ng/mL. Both forms of G-CSF increased the percentage of CD11b positive cells in Kasumi-1 cells.

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