Gene therapy of murine teratocarcinoma: separate functions for insulin-like growth factors I and II in immunogenicity and differentiation.
Teratocarcinoma is a germ-line carcinoma giving rise to an embryoid tumor with structures derived from the three embryonic layers: mesoderm, endoderm, and ectoderm. Teratocarcinoma is widely used as an in vitro model system to study regulation of cell determination and differentiation during mammalian embryogenesis. Murine embryonic carcinoma (EC) PCC3 cells express insulin-like growth factor I(IGF-I) and its receptor, while all derivative tumor structures express IGF-I and IGF-II and their receptors. Therefore the system lends itself to dissect the role of these two growth factors during EC differentiation. With an episomal antisense strategy, we define a role for IGF-I in tumorigenicity and evasion of immune surveillance. Antisense IGF-I EC transfectants are shown to elicit a curative anti-tumor immune response with tumor regression at distal sites. In contrast, IGF-II is shown to drive determination and differentiation in EC cells. Since IGF-I and IGF-II bind to type I receptor and antisense sequence used for IGF-II cannot form duplex with endogenous IGF-I transcripts, it follows that this receptor is not involved in determination and differentiation.
Trojan
J
J
Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4943.
Johnson
T R
TR
Rudin
S D
SD
Blossey
B K
BK
Kelley
K M
KM
Shevelev
A
A
Abdul-Karim
F W
FW
Anthony
D D
DD
Tykocinski
M L
ML
Ilan
J
J
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects*; D015870:Gene Expression; D015316:Genetic Therapy; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D007335:Insulin-Like Growth Factor II / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D015183:Restriction Mapping; D018243:Teratocarcinoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D014407:Tumor Cells, Cultured
D016376:Oligonucleotides, Antisense; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II