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

Abstract

BackgroundGranulocyte-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.MethodsWe 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.ResultsG-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.ConclusionThe 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.

Recombinant Human Granulocyte Colony-Stimulating Factor Promotes Preinvasive and Invasive Estrogen Receptor-Positive Tumor Development in MMTV-erbB2 Mice

“…Moon et al [ 28 ] were the first to reveal proliferation and differentiation in leukemia and solid tumor cells using 38 solid tumor cell lines and five hematopoietic cell lines. They found that G-CSF stimulated proliferation (40%-80% increase in proliferation in treated cells compared with that in control cells) in three leukemic cell lines and induced differentiation of AML1/ETO+ leukemic cells.…”

A role for G‐CSF and GM‐CSF in nonmyeloid cancers

“…That necessitates their consideration in a differential diagnosis given the use of adjuvant GM‐CSF in these patients . Melanoma cells in vitro have been found to express G‐CSFR transcript; increases in cell proliferation, however, do not occur upon G‐CSF stimulation possibly reflecting an absence of a G‐CSFR protein . In contrast, a role of GM‐CSF in dissemination of melanoma is controversial.…”

A New Function of Granulocyte Colony-stimulating Factor (G-CSF): Suppression of Cell Proliferation in Uterine Endometrial Carcinoma

“…G-CSF is known to induce proliferation in various cell types via G-CSF-R, and different signal-transduction pathways can be induced depending on the different binding sites of G-CSF-R [21]. The Jak-Stat pathway is one signaling pathway that regulates cell proliferation by G-CSF via G-CSF-R [9][10][11]. We analyzed the effect of G-CSF on the mRNA-expression level of suppressor of cytokine signaling (SOCS)-3, which is a negative regulator of G-CSF-R and down-regulates G-CSF signaling [22].…”

“…The mRNA-expression levels of ER in both cell lines did not show any significant difference in any group (Figure 4C, 4F). G-CSF can induce cell proliferation in many normal cell types (including normal chorionic cells) and in cancer cells [9,11]. In contrast, the only report showing that G-CSF suppressed cell proliferation was performed with BeWo (culture condition: 2.5-10% serum) and JEG-3 (2.5% serum) human choriocarcinoma cells (half-maximal effect of G-CSF observed at 30-50 ng/ml) [13] in agreement with the present report (however, Marino et al showed that JEG-3 cell proliferation increased after administration of 1 g/ml  of G-CSF in culture medium containing 0.5% serum [14]).…”

“…However, the function of G-CSF-R is not fully understood yet. It has been reported that G-CSF induces cell proliferation via G-CSF-R in various cell types, including leukemia, bladder cancer, and glioma cells [9][10][11]. Regarding the female reproductive system, it was reported that G-CSF induced cell proliferation in normal chorionic cells [12].…”