期刊
CANCER RESEARCH
卷 64, 期 10, 页码 3380-3385出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-03-3780
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The receptor for the type 1 insulin-like growth factor (IGF-IR) was identified as a major regulator of the malignant phenotype and a target for cancer therapy. In the present study, a novel IGF-IR mutant consisting of the entire extracellular domain of the receptor (IGFIR(933)) was genetically engineered and expressed in highly metastatic H-59 murine lung carcinoma cells. We show here that the cells expressed a truncated heterotetramer (beta(m)-alpha-alpha-beta(m) ) that was secreted into the medium and could neutralize the effects of exogenous IGF-I, thus diminishing IGF-I-induced signaling and blocking IGF-I-mediated cellular functions such as cell proliferation, invasion, and survival. In vivo, tumor incidence and growth rate were markedly reduced in mice inoculated s.c. with H-59/IGFIR(933) cells. Moreover, after the intrasplenic/portal inoculation of these cells, there was a 90% reduction in the incidence of hepatic metastases and a significant increase in the long-term, disease-free survival of the mice compared with controls. Our results identify the IGFIR(933) as a potent antitumorigenic and antimetastatic agent with potential applications for cancer gene therapy.
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