Mr. Chicoine et al., MODIFICATION OF HUMAN GLIOMA LOCOMOTION IN-VITRO BY CYTOKINES EGF, BFGF, PDGFBB, NGF, AND TNF-ALPHA, Neurosurgery, 36(6), 1995, pp. 1165-1170
CYTOKINES EXERT RECEPTOR-MEDIATED control over glia. Up-regulation of
receptor expression or cytokine production corresponds with the acquis
ition 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, th
e 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 mi agar
(50 ng/ml if the cytokine was distributed evenly throughout the dish)
at one edge, and 0.5 mi plain agar at the opposite edge. After 24 hou
rs, 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 cytok
ine gradient and the plain agar. The epidermal growth factor caused co
ntinuous chemoattraction, whereas the tumor necrosis factor alpha caus
ed slight chemorepulsion for 24 to 48 hours, followed by strong chemoa
ttraction. The bb dimer of platelet-derived growth factor, the basic f
ibroblast growth factor, and the nerve growth factor all maintained ch
emorepulsion over the entire 6 to 10 days. Therefore, the cytokines di
d affect glioma cell motility in vitro, and the modified radial dish a
ssay used in this study provided a useful in vitro model for assessing
the impact of the cytokines on glioma cell locomotion. Further unders
tanding of this phenomenon might facilitate the development of therapi
es to limit glioma cell locomotion and invasion.