Cell proliferation and migration in glioblastoma multiforme cell lines are influenced by insulin-like growth factor I in vitro.
BACKGROUND
Malignant gliomas continue to be a therapeutic challenge. One of the major problems is the early and rapidly infiltrating tumor growth. The role of the insulinlike growth factor (IGF) system in the progression of malignant glioma growth is poorly understood. In this study we investigated the expression of different members of the IGF system in malignant glioma cells and the influence of IGF-I and -II on the proliferation and migration of human glioma cell lines in vitro.


METHODS
Expression of IGF-I and -II, IGF-receptor I and II and IGF binding proteins (IGFBP) 1 to 6 was analysed by PCR in cell lines T98G, A172, 86HG39 (glioblastoma multiforme) and U87MG (anaplastic astrocytoma). To investigate effects on cell-proliferation, the cells were treated with IGF-I or -II (0.001-100 ng/ml). The cell viability was assessed by MTT-assay. For testing migratory effects, the Boyden-chamber-assay with different combinations of IGF-I or -II or fetal calf serum (FCS) as chemotactic agents was used.


RESULTS
All cell lines expressed IGF-I- and IGF-II-receptor, whereas none of the cells expressed IGF-I or -II. IGFBP 2-6 were found in all cell lines. IGF-I treated cell lines T98G and 86HG39 showed a weak dose-independent enhanced proliferation compared to controls, whereas A172 did not respond. None of the investigated cell lines changed proliferation when treated with IGF-II. All IGF-I (100 ng/ml) treated cells showed increased migration compared to controls. This effect was markedly enhanced by supplementation with 0.5% FCS. Again, IGF-II had no effect.


CONCLUSIONS
These data demonstrate that IGF-I modulates proliferation and strongly stimulates migration of glioma cell lines in vitro.
Schlenska-Lange
Anke
A
Hospital for Children and Adolescents, University of Leipzig, Liebigstr. 20 a, D-04103 Leipzig, Germany.
Knüpfer
Heike
H
Lange
Tobias J
TJ
Kiess
Wieland
W
Knüpfer
Matthias
M
D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000378:metabolism; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000378:metabolism; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D007335:Insulin-Like Growth Factor II / Q000502:physiology*; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D017527:Receptor, IGF Type 2 / Q000378:metabolism
D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D018976:Insulin-Like Growth Factor Binding Protein 6; D018969:Insulin-Like Growth Factor Binding Proteins; D017527:Receptor, IGF Type 2; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1