Etiology and Pathogenesis > Insulin-like Growth Factors

Abstract

Inhibition of tumor growth by a dominant negative mutant of the insulin-like growth factor I receptor with a bystander effect

Reiss K, D'Ambrosio C, Tu X, Tu C, Baserga R

Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA

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.

PMID: 9829727 [PubMed - indexed for MEDLINE]