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Antitumor Effects of a Soluble Insulin-Like Growth Factor I Receptor in Human Ovarian Cancer Cells

Advantage of Recombinant Protein Administration in Vivo

Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan

Antitumor effects of a soluble form dominant negative of the type I insulin-like growth factor receptor (IGF-IR) designated as 486/STOP were evaluated in CaOV-3 human ovarian cancer cells by establishing stable transformants overexpressing 486/STOP and by administration of 486/STOP recombinant protein. Expression of 486/STOP was detected from total cell lysates, as well as conditioned media collected from stable transformants. In stable transformants, growth in monolayer was slightly retarded, and anchorage-independent growth in vitro and tumorigenicity in vivo were markedly inhibited. Addition of conditioned media from 486/STOP cells inhibited anchorage-independent growth of parental cells. Although tumorigenicity of parental cells in vivo was abrogated when they were cocultured in monolayer with 486/STOP cells over 48 h before injection to nude mice, coinjection of parental cells and 486/STOP cells without preculture was not successful. In contrast, administration of 486/STOP partially purified recombinant protein inhibited tumorigenicity of parental cells in vivo. Because 486/STOP cells result in massive apoptosis in vivo within 48 h, usage of a recombinant protein has a great advantage to use its unique bystander effect in vivo for clinical application.

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