Up-Regulation of Imp3 Confers In Vivo Tumorigenicity on Murine Osteosarcoma Cells

Arisa Ueki, Takatsune Shimizu, Kenta Masuda, Sayaka I. Yamaguchi, Tomoki Ishikawa, Eiji Sugihara, Nobuyuki Onishi, Shinji Kuninaka, Keita Miyoshi, Akihiro Muto, Yoshiaki Toyama, Kouji Banno, Daisuke Aoki, Hideyuki Saya

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article numbere50621
JournalPLoS One
Volume7
Issue number11
DOIs
Publication statusPublished - 2012 Nov 30

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osteosarcoma
Osteosarcoma
Tumors
Up-Regulation
Messenger RNA
mice
cells
neoplasms
Neoplasms
Anoikis
Contact Inhibition
Bone
Aptitude
Neoplastic Stem Cells
Molecules
bones
Bone and Bones
therapeutics
stems

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Up-Regulation of Imp3 Confers In Vivo Tumorigenicity on Murine Osteosarcoma Cells. / Ueki, Arisa; Shimizu, Takatsune; Masuda, Kenta; Yamaguchi, Sayaka I.; Ishikawa, Tomoki; Sugihara, Eiji; Onishi, Nobuyuki; Kuninaka, Shinji; Miyoshi, Keita; Muto, Akihiro; Toyama, Yoshiaki; Banno, Kouji; Aoki, Daisuke; Saya, Hideyuki.

In: PLoS One, Vol. 7, No. 11, e50621, 30.11.2012.

Research output: Contribution to journalArticle

Ueki, A, Shimizu, T, Masuda, K, Yamaguchi, SI, Ishikawa, T, Sugihara, E, Onishi, N, Kuninaka, S, Miyoshi, K, Muto, A, Toyama, Y, Banno, K, Aoki, D & Saya, H 2012, 'Up-Regulation of Imp3 Confers In Vivo Tumorigenicity on Murine Osteosarcoma Cells', PLoS One, vol. 7, no. 11, e50621. https://doi.org/10.1371/journal.pone.0050621
Ueki, Arisa ; Shimizu, Takatsune ; Masuda, Kenta ; Yamaguchi, Sayaka I. ; Ishikawa, Tomoki ; Sugihara, Eiji ; Onishi, Nobuyuki ; Kuninaka, Shinji ; Miyoshi, Keita ; Muto, Akihiro ; Toyama, Yoshiaki ; Banno, Kouji ; Aoki, Daisuke ; Saya, Hideyuki. / Up-Regulation of Imp3 Confers In Vivo Tumorigenicity on Murine Osteosarcoma Cells. In: PLoS One. 2012 ; Vol. 7, No. 11.
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