Expressions of G-CSF Receptor in Tumor Cells Might Stimulate the Proliferation of Malignant Cells Upon Treatment of G-CSF.

Abstract 1009

Poster Board I-31

We previously reported that the increased expression of G-CSFR in AML1/ETO⁺ AML cell, suggesting that cells with G-CSFR expression might easily proliferate in response to therapeutic G-CSF. To confirm the association of AML/ETO gene and increased expression of G-CSFR, we transfected AML1/ETO specific small interfering RNAs (siRNAs) to AML/ETO⁺ cell line and G-CSFR expression was decreased on transfection by siRNA AML1/ETO gene suggesting a strong association between AML1/ETO gene and G-CSFR up-regulation. To assess the effect of G-CSF on G-CSR expressing leukemic cells, we treated the most commonly used two forms of G-CSF on various leukemic cell lines. Both forms of G-CSF significantly stimulated the cell proliferation (40-80% increment compared to control) and the differentiation of AML1/ETO⁺ leukemic cells. Western blot showed marked increased signals of JAK2/STAT3 after treatment of G-CSF on AML/ETO⁺ Kasumi-1 cell line, while there was no increased signals in AML/ETO^- CTV-1 cell line. To search the malignant tumors with increased G-CSFR, we screened the expressions of G-CSFR mRNA in 32 kinds of solid tumor cell lines and % kinds of leukemic cell lines, using real-time PCR. Among 32 kinds of solid tumor cell lines, 3 cell lines [hepatoblastoma (HepG2), squamous cell carcinoma of larynx (SNU-899), and breast carcinoma cell line (MCF 10A)] expressed G-CSFR mRNA and amount of G-CSFR expression of HepG2 cell was comparable to Kasumi-1 cell lines. In summary, association of G-CSFR and AML/ETO gene is strongly suggested. Expression of G-CSFR in some tumor cells is suspected, requiring pre-screening of G-CSFR expression before treatment of G-CSF. The present study shows that therapeutic G-CSF might stimulate the proliferation and differentiation of malignant cells with G-CSFR expression (AML/ETO⁺ AML cell and solid tumor cell lines) and we suggest the prescreening of G-CSFR expression primary tumor cells before treatment of G-CSF.