Rat glioblastoma cells expressing an antisense
RNA to the insulin-like growth factor-1 (IGF-1) receptor are nontumorigenic and
induce regression of wild-type tumors
Resnicoff M, Sell C, Rubini M, Coppola D, Ambrose D, Baserga R, Rubin R
Department of Pathology and Cell Biology, Jefferson Medical
College, Philadelphia, Pennsylvania 19107
Insulin-like growth factor-1 (IGF-1) and IGF-2 are critical regulators of cell
The growth-promoting action of both ligands is mediated by the type 1 IGF
We have investigated the role of the IGF-1R in the growth and tumorigenicity of
rat C6 glioblastoma cells.
For this purpose, antisense RNA to IGF-1R RNA was introduced into cells by
either the addition of oligodeoxynucleotides or by transfection with plasmids
that express antisense RNA to IGF-1R RNA.
At low cell density, C6 cells grew slowly in serum-free medium and proliferated
with the sole addition of IGF-1 or IGF-2.
Both antisense IGF-1R oligodeoxynucleotides and stable transfection with a
plasmid expressing an antisense IGF-1R RNA inhibited IGF-1-mediated growth in
monolayers and clonogenicity in soft agar.
Sense oligodeoxynucleotides and sense-expressing plasmid had no effect on either
In stable antisense transfectants, tyrosine-phosphorylated IGF-1 receptors were
not detectable, although they were easily detected in wild-type cells.
When wild-type C6 cells were injected s.c. into syngeneic immunocompetent rats,
tumors developed within 1 week.
In contrast, stably transfected C6 cells overexpressing antisense IGF-1R RNA
Moreover, when C6 IGF-1R antisense cells were injected, subsequent tumor
formation by wild-type C6 cells was completely prevented.
Finally, injection of C6 IGF-1R antisense cells into rats carrying an
established wild-type C6 tumor caused complete regression of the tumors.
The results demonstrate the critical importance of the IGF-1R in glioblastoma
cell growth, clonogenicity, and tumorigenicity.
Although the mechanism is presently unknown, the fact that the injection of C6
cells expressing an antisense RNA to IGF-1R RNA leads to regression of already
established wild-type C6 tumors suggests the possibility of practical
PMID: 8174129 [PubMed - indexed for MEDLINE]