Autocrine growth regulation by granulocyte colony-stimulating factor and granulocyte macrophage colony-stimulating factor in human gliomas with tumorprogression

Granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage co lony-stimulating factor (GM-CSF) and/or their receptors are increasingly de tected in solid human tumors, although Little is known about their function in tumor growth and invasion. We analyzed RNA and protein expression of bo th factors and their receptors in 22 human gliomas (WHO grade II, III, and IV) and derived cell cultures. G-CSF, GM-CSF, and/or their receptors were e xpressed in all tumors and derived cell cultures, but coexpression of both factors and receptors was almost exclusively found in grade IV glioblastoma s and thus correlated with advanced tumor stage. The functional significanc e of G-CSF and GM-CSF as regulators for glioma cells was demonstrated by 1) stimulation of proliferation and migration in tumor cells expressing one o r both receptors by the corresponding factor; 2) inhibition of growth and m igration of glioma cells expressing G-CSF, GM-CSF, and their receptors by n eutralizing antibodies to both factors. These results indicate a significan t role for both factors in the autocrine regulation of growth and migration in late-stage malignant gliomas and suggest a shift from paracrine to auto crine regulation with tumor progression. The implication of G-CSF and GM-CS F in glioblastoma growth regulation could make these factors further progno stic indicators and raises questions concerning their use in cancer therapy .