title: Up-regulation of Imp3 confers in vivo tumorigenicity on murine osteosarcoma cells.
abstract: Osteosarcoma is a high-grade malignant bone tumor that manifests ingravescent clinical behavior. The intrinsic events that confer malignant properties on osteosarcoma cells have remained unclear, however. We previously established two lines of mouse osteosarcoma cells: AX cells, which are able to form tumors in syngeneic mice, and AXT cells, which were derived from such tumors and acquired an increased tumorigenic capacity during tumor development. We have now identified Igf2 mRNA-binding protein3 (Imp3) as a key molecule responsible for this increased tumorigenicity of AXT cells in vivo. Imp3 is consistently up-regulated in tumors formed by AX cells, and its expression in these cells was found to confer malignant properties such as anchorage-independent growth, loss of contact inhibition, and escape from anoikis in vitro. The expression level of Imp3 also appeared directly related to tumorigenic ability in vivo which is the critical determination for tumor-initiating cells. The effect of Imp3 on tumorigenicity of osteosarcoma cells did not appear to be mediated through Igf2-dependent mechanism. Our results implicate Imp3 as a key regulator of stem-like tumorigenic characteristics in osteosarcoma cells and as a potential therapeutic target for this malignancy.
authors.affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Arisa
authors.initials: A
authors.lastname: Ueki
authors.forename: Takatsune
authors.initials: T
authors.lastname: Shimizu
authors.forename: Kenta
authors.initials: K
authors.lastname: Masuda
authors.forename: Sayaka I
authors.initials: SI
authors.lastname: Yamaguchi
authors.forename: Tomoki
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Eiji
authors.initials: E
authors.lastname: Sugihara
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Onishi
authors.forename: Shinji
authors.initials: S
authors.lastname: Kuninaka
authors.forename: Keita
authors.initials: K
authors.lastname: Miyoshi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Muto
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.forename: Kouji
authors.initials: K
authors.lastname: Banno
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saya
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology*; D010641:Phenotype; D016601:RNA-Binding Proteins / Q000235:genetics*; D015854:Up-Regulation
chemical_list: C498780:IGF2BP3 protein, human; C498777:Igf2bp3 protein, mouse; D016601:RNA-Binding Proteins