Correlation of glioma cell regression with inhibition of insulin-like growth factor 1 and insulin-like growth factor-binding protein-2 expression.
To explore the antitumor effect of insulin-like growth factor 1 (IGF-I) antisense RNA and the interaction of IGF-I with insulin-like growth factor-binding proteins (IGFBPs) in glioma cells, a recombinant retrovirus expressing IGF-I antisense RNA was constructed and introduced into C6 glioma cells. IGF-I antisense RNA reverses the transformed phenotype in glioma cells and inhibits glioma cell growth by blocking overexpression of endogenous IGF-I. Expression of IGFBP-2 is increased in glioma cells as compared with normal adult glial cells. IGF-I antisense RNA also inhibits expression of IGFBP-2 in glioma cells, but does not influence expression of the other IGFBPs. Although IGFBP-2 in conditioned medium from wild-type C6 cell cultures itself does not directly influence glioma cell growth, it synergistically enhances exogenous IGF-I-mediated DNA synthesis in IGF-I-negative C6 cells. These findings indicate the inhibitory effect of IGF-I antisense RNA on growth and development of glioma cells. IGF-I-dependent glioma cell growth may, in some circumstances, require IGFBP-2 as a cofactor. The antitumor effect of IGF-I antisense RNA is also associated with inhibition of IGFBP-2 expression.
Wang
Z H
ZH
Department of Neurology, New York University School of Medicine, New York 10016, USA.
Ma
J
J
Zeng
B J
BJ
Catanese
V M
VM
Samuels
S
S
Gama Sosa
M A
MA
Kolodny
E H
EH
D000818:Animals; D002455:Cell Division / Q000502:physiology; D002461:Cell Line, Transformed; D002470:Cell Survival; D017077:Culture Media, Conditioned; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005822:Genetic Vectors; D005910:Glioma / Q000473:pathology / Q000628:therapy*; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D010641:Phenotype; D016372:RNA, Antisense / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012190:Retroviridae / Q000235:genetics; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D004273:DNA, Neoplasm; D018971:Insulin-Like Growth Factor Binding Protein 2; D016372:RNA, Antisense; D007334:Insulin-Like Growth Factor I