Conversion of glioma cells to glioma stem-like cells by angiocrine factors

Jun Kyum Kim, Hye Min Jeon, Hee Young Jeon, Se Yeong Oh, Eun Jung Kim, Xiong Jin, Se Hoon Kim, Sung Hak Kim, Xun Jin, Hyunggee Kim

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Abstract

Glioma stem-like cells (GSCs) contribute to tumor initiation, progression, and therapeutic resistance, but their cellular origin remains largely unknown. Here, using a stem/progenitor cell-fate tracking reporter system in which eGFP is expressed by promoter of OCT4 that is activated in stem/progenitor cells, we demonstrate that eGFP-negative glioma cells (GCs) became eGFP-positive-GCs in both in vitro cultures and in vivo xenografts. These eGFP-positive-GCs exhibited GSC features and primarily localized to the perivascular region in tumor xenografts, similar to the existence of OCT4-expressing GCs in the perivascular region of human glioblastoma specimens. Angiocrine factors, including nitric oxide (NO), converted eGFP-negative-GCs into eGFP-positive-GCs. Mechanistically, NO signaling conferred GSC features to GCs by increasing OCT4 and NOTCH signaling via ID4. NO signaling blockade and a suicide gene induction prevented tumorigenicity with a decrease in eGFP-positive-GCs in the perivascular region. Taken together, our results reveal the molecular mechanism underlying GSCs generation by cancer cell dedifferentiation.

Original languageEnglish
JournalBiochemical and Biophysical Research Communications
DOIs
Publication statusAccepted/In press - 2017 Jan 26

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Keywords

  • Angiocrine factors
  • Glioma cells
  • Glioma stem-like cells
  • ID4
  • OCT4

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Kim, J. K., Jeon, H. M., Jeon, H. Y., Oh, S. Y., Kim, E. J., Jin, X., Kim, S. H., Kim, S. H., Jin, X., & Kim, H. (Accepted/In press). Conversion of glioma cells to glioma stem-like cells by angiocrine factors. Biochemical and Biophysical Research Communications. https://doi.org/10.1016/j.bbrc.2017.02.076