Modification of Human Glioma Locomotion In Vitro by Cytokines EGF, bFGF, PDGFbb, NGF, and TNFα

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Abstract
CYTOKINES EXERT RECEPTOR-MEDIATED control over glia. Up-regulation of receptor expression or cytokine production corresponds with the acquisition of a neoplastic phenotype. A modified radial dish assay was used to determine whether in vitro locomotion of glioma cells is modified by the epidermal growth factor, the basic fibroblast growth factor, the bb dimer of platelet-derived growth factor, the nerve growth factor, or the tumor necrosis factor alpha. Human glioma cells were plated in the center of a petri dish with one of these cytokines in 0.5 ml agar (50 ng/ml if the cytokine was distributed evenly throughout the dish) at one edge, and 0.5 ml plain agar at the opposite edge. After 24 hours, a central zone of cells was established; the agar was gelatinized. Feeding medium was added to the dish, and slow elution from the agar established a cytokine gradient. Cell counts were performed daily over 6 to 10 days at predetermined distances on both sides of the central zone to assess directional cellular movement with respect to the cytokine gradient and the plain agar. The epidermal growth factor caused continuous chemoattraction, whereas the tumor necrosis factor alpha caused slight chemorepulsion for 24 to 48 hours, followed by strong chemoattraction. The bb dimer of platelet-derived growth factor, the basic fibroblast growth factor, and the nerve growth factor all maintained chemorepulsion over the entire 6 to 10 days. Therefore, the cytokines did affect glioma cell motility in vitro, and the modified radial dish assay used in this study provided a useful in vitro model for assessing the impact of the cytokines on glioma cell locomotion. Further understanding of this phenomenon might facilitate the development of therapies to limit glioma cell locomotion and invasion.