Effect of recombinant tumor necrosis factor-alpha on three-dimensional growth, morphology, and invasiveness of human glioblastoma cells in vitro.
In order to investigate the antiproliferative and anti-invasive effects of tumor necrosis factor (TNF)-alpha on human glioblastoma cells, an in vitro three-dimensional (anchorage-independent) assay was performed using Matrigel, a mixture of extracellular matrix proteins. Four glioblastoma-derived cell lines, including one cloned line, were cultured in Matrigel with or without TNF-alpha. In the Matrigel containing TNF-alpha, three of the four cell lines, including the cloned line, showed significant growth inhibition in a dose-dependent manner. Dramatic three-dimensional morphological differences were observed between TNF-treated and untreated glioblastoma cells cultured in Matrigel. Untreated cells formed large and highly branched colonies throughout the gel. In contrast, the majority of TNF-treated cells demonstrated truncated branching processes and, at a high TNF-alpha dose, an increasing number of cells remained in relatively small spherical aggregates, their cell processes being significantly reduced. Quantitative invasion assay using a micro-Boyden chamber system confirmed that TNF-treated cells lost invasiveness in a dose-dependent manner. These results suggest that TNF-alpha exerts not only antiproliferative but also anti-invasive effects on human glioblastoma cells in vitro. It is believed that this is the first report showing the anti-invasive effect of TNF-alpha on tumor cells.
Iwasaki
K
K
Department of Neurology, Cleveland Clinic Foundation, Ohio.
Rogers
L R
LR
Barnett
G H
GH
Estes
M L
ML
Barna
B P
BP
D001932:Brain Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002999:Clone Cells; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D005910:Glioma / Q000473:pathology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma