Erythropoietin and G-CSF receptors in human tumor cells: Expression and aspects regarding functionality

Aims and background: Recombinant human erythropoietin (Epo) and granulocyte-colony-stimulating factor (G-CSF) are used to stimulate hematopoiesis in patients with malignant diseases. These cytokines transduce their biological signal via the Epo receptor (EpoR) and G-CSF receptor (G-CSF-R) into the cell. We therefore investigated in human tumor cell lines the expression of these receptors in tumor cells as well as their response to Epo and G-CSF. Methods and study design: The expression of EpoR and G-CSF-R mRNA was analyzed with reverse transcription-polymerase chain reaction (RT-PCR). EpoR protein expression was further monitored with Western blot and immunocytochemistry analysis. The cellular response to various concentrations of Epo was evaluated using (3)[H]-thymidine uptake, Northern blot of c-fos expression and tyrosine kinase activity assay. The proliferation after G-CSF incubation was analyzed with the NITS assay. Results: In this study EpoR mRNA and protein were detected in various human tumor cell lines. Treatment with Epo did not influence the proliferation rate of examined EpoR-positive tumor cell lines. Epo did not stimulate the tyrosine kinase activity nor did it affect the c-fos mRNA In these cell lines. G-CSF-R mRNA was only detected In two myeloid cell lines. Treatment with G-CSF did not Increase the proliferation of these cells. Conclusions: These results demonstrate that Epo and G-CSF did not modulate the growth rate of examined receptor-positive tumor cell lines; the presence of the Epo receptor seems not essential for cell growth of these tumor cells In cell culture.