Extrinsic ribosome stimuli triggers development of glioblastoma stem like cells

DOI Web Site Open Access
  • Jono Hirofumi
    Kumamoto University Hospital Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Shirakawa Yuki
    Graduate School of Medicine, Juntendo University
  • Miyake Shunsuke
    Kumamoto University Hospital Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Kanemaru Ayumi
    Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Yonemaru Kou
    Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Uchino Shota
    Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Hide Takuichiro
    Kitasato University School of Medicine
  • Mukasa Akitake
    Graduate School of Medical Sciences, Kumamoto University
  • Ohta Kunimasa
    Faculty of Arts and Science, Kyushu University
  • Saito Hideyuki
    Kumamoto University Hospital Graduate School of Pharmaceutical Sciences, Kumamoto University

Bibliographic Information

Other Title
  • 外因性リボゾームによる膠芽腫がん幹細胞様細胞の発生メカニズムの解明

Description

<p>Background: Although glioblastoma (GBM) stem like cells (GSCs), which exhibit chemo-radio resistance and recurrence, are key prognostic factors in GBM patients, molecular mechanisms of GSCs development are largely unknown. Recent studies revealed that extrinsic ribosome incorporation into somatic cells played key roles in cell reprogramming process towards stem cell properties. In this study, we sought to elucidate the mechanisms underlying GSCs development by focusing extrinsic ribosome incorporation into GBM cells. </p><p>Results: The ribosome incorporation into GBM cells significantly increased ribosome induced cancer cell spheroid (RICCS) formation, and showed the stem like cell characters. In RICCS, phosphorylation and protein expression of RPS6, an intrinsic ribosomal protein, and STAT3 phosphorylation were involved in regulating cell spheroids formation. Interestingly, glioma-derived extrinsic ribosome also promoted GBM-RICCS formation through the intrinsic RPS6 phosphorylation. Moreover, in glioma patients, RPS6 phosphorylation was observed in higher grade glioma tissues, and predominantly up-regulated in GSCs niches, such as perinecrosis niche and perivascular niche. </p><p>Conclusion: Our results suggest the potential biological & clinical significance of extrinsic ribosomal proteins in GSCs development.</p>

Journal

Keywords

Details 詳細情報について

Report a problem

Back to top