Human glioblastoma cells produce granulocyte-macrophage colony-stimulating factor in vitro, but not in vivo, without expressing its receptor.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) production and receptor expression by human glioblastomas was studied. Enzyme-linked immunosorbent assay showed four of 10 glioblastoma cell lines spontaneously released GM-CSF (2.9-9.2 pg GM-CSF protein/ml culture medium), which was enhanced by stimulation with tumor necrosis factor-alpha (TNF) (10 U/ml) up to 410 pg/ml. TNF also induced secretion of GM-CSF by another cell line. Northern blot analysis identified increasing GM-CSF gene expression by cells following TNF stimulation. However, no GM-CSF protein was detectable in the cerebrospinal fluid of three malignant glioma patients. Intratumoral administration of TNF in the patients also failed to stimulate GM-CSF levels in the cerebrospinal fluid. A binding assay using flow cytometry with biotinylated GM-CSF and Scatchard analysis using 125I-labeled GM-CSF failed to demonstrate GM-CSF receptor expression on the 13 cell lines. Exogenous GM-CSF stimulation had no effect on production of prostaglandin E2, interleukin-6, or interleukin-8 by glioma cells. Human glioblastoma cells secrete GM-CSF without expressing the receptor in vitro, but there was no evidence of GM-CSF production in vivo.
Murata
J
J
Department of Neurosurgery, Hokkaido University School of Medicine, Sapporo.
Sawamura
Y
Y
Tada
M
M
Sakuma
S
S
Sudo
M
M
Aida
T
T
Abe
H
H
D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D006801:Humans; D007231:Infant, Newborn; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor