Antitumor effects of a soluble insulin-like growth factor I receptor in human ovarian cancer cells: advantage of recombinant protein administration in vivo.
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.
Hongo
Atsushi
A
Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata, Okayama 700-8558, Japan. hongo1@cc.okayama-u.ac.jp
Kuramoto
Hiroyuki
H
Nakamura
Yojiro
Y
Hasegawa
Kosei
K
Nakamura
Keiichiro
K
Kodama
Junichi
J
Hiramatsu
Yuji
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
D017077:Culture Media, Conditioned; D011994:Recombinant Proteins; D017526:Receptor, IGF Type 1