EFFECT OF RECOMBINANT TUMOR-NECROSIS-FACTOR-ALPHA ON 3-DIMENSIONAL GROWTH, MORPHOLOGY, AND INVASIVENESS OF HUMAN GLIOBLASTOMA CELLS-INVITRO

In order to investigate the antiproliferative and anti-invasive effect s of tumor necrosis factor (TNF)-alpha on human glioblastoma cells, an in vitro three-dimensional (anchorage-independent) assay was performe d using Matrigel, a mixture of extracellular matrix proteins. Four gli oblastoma-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, showe d significant growth inhibition in a dose-dependent manner. Dramatic t hree-dimensional morphological differences were observed between TNF-t reated and untreated glioblastoma cells cultured in Matrigel. Untreate d 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 numbe r of cells remained in relatively small spherical aggregates, their ce ll processes being significantly reduced. Quantitative invasion assay using a micro-Boyden chamber system confirmed that TNF-treated cells l ost invasiveness in a dose-dependent manner. These results suggest tha t TNF-alpha exerts not only antiproliferative but also anti-invasive e ffects on human glioblastoma cells in vitro. It is believed that this is the first report showing the anti-invasive effect of TNF-alpha on t umor cells.