Inhibition of tumor growth by a dominant negative mutant of the insulin-like growth factor I receptor with a bystander effect.
The insulin-like growth factor I receptor is known to play a major role in transformation and apoptosis. The dominant negative mutant of the insulin-like growth factor I receptor, designated 486/STOP, causes massive apoptosis of tumor cells and inhibition of tumor growth and metastases. We now show that: (a) the stable expression of 486/STOP inhibits transformation (colony formation in soft agar) and/or tumor growth in nude mice of five different types of human tumor cell lines; and (b) more importantly, it has a bystander effect, inhibiting the growth of wild-type tumor cells when cells expressing 486/STOP are coinjected with wild-type tumor cells. These findings suggest that it is not necessary to infect all tumor cells with 486/STOP to inhibit tumor growth, and they also open the possibility of using the product of 486/STOP directly against tumor cells.
Reiss
K
K
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
D'Ambrosio
C
C
Tu
X
X
Tu
C
C
Baserga
R
R
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D017077:Culture Media, Conditioned; D005799:Genes, Dominant; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010957:Plasmids / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D017077:Culture Media, Conditioned; D017526:Receptor, IGF Type 1