Medulloblastoma Cells Constitutively Produce Granulocyte Colony-Stimulating Factor*

Abstract

Granulocyte colony-stimulating factor (G-CSF) was previously shown to be produced constitutively by malignant epithelial cells and by monocytes/macrophages, fibroblasts and endothelial cells following stimulation. In this study we investigated the ability of medulloblastoma cells, representing malignant embryonal neuroectodermal cells, to produce G-CSF. Conditioned medium was freshly prepared from unstimulated explanted tumor tissue from two patients with medulloblastoma as well as from the medulloblastoma cell lines TE-671 and DAOY, and as controls normal glial cells. Following 72 hours of culture at a density of 5 x 10(5) cells/ml in RPMI 1640 with 10% FCS, the supernatants were harvested and tested for the presence of G-CSF in (1) the CFU-GM asay, (2) proliferation assay using the G-CSF dependent cell line NFS-60, and (3) Western blot analysis using an anti-G-CSF monoclonal antibody. Biological active and immunological detectable G-CSF was secreted by the medulloblastoma cell line DAOY and by one of the explanted tumor biopsies. The cell line TE-671 as well as normal glial cells did not produce G-CSF under identical culture conditions. We conclude that in addition to previously described sources of G-CSF, neuroectodermally derived medulloblastoma cells are also able to produce G-CSF constitutively. The G-CSF production was increased after stimulation with IL-1 alpha or TNF alpha. The role of G-CSF in neuroectodermal tissues remains to be further investigated.