Recruited brain tumor-derived mesenchymal stem cells contribute to brain tumor progression

Jinan Behnan, Pauline Isakson, Mrinal Joel, Corrado Cilio, Iver A. Langmoen, Einar O. Vik-Mo, Wiaam Badn

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

The identity of the cells that contribute to brain tumor structure and progression remains unclear. Mesenchymal stem cells (MSCs) have recently been isolated from normal mouse brain. Here, we report the infiltration of MSC-like cells into the GL261 murine glioma model. These brain tumor-derived mesenchymal stem cells (BT-MSCs) are defined with the phenotype (Lin-Sca-1+CD9+CD44+CD166+/- ) and have multipotent differentiation capacity. We show that the infiltration of BT-MSCs correlates to tumor progression; furthermore, BT-MSCs increased the proliferation rate of GL261 cells in vitro. For the first time, we report that the majority of GL261 cells expressed mesenchymal phenotype under both adherent and sphere culture conditions in vitro and that the non-MSC population is nontumorigenic in vivo. Although the GL261 cell line expressed mesenchymal phenotype markers in vitro, most BT-MSCs are recruited cells from host origin in both wild-type GL261 inoculated into green fluorescent protein (GFP)-transgenic mice and GL261-GFP cells inoculated into wild-type mice. We show the expression of chemokine receptors CXCR4 and CXCR6 on different recruited cell populations. In vivo, the GL261 cells change marker profile and acquire a phenotype that is more similar to cells growing in sphere culture conditions. Finally, we identify a BT-MSC population in human glioblastoma that is CD44+CD9+CD166+ both in freshly isolated and culture-expanded cells. Our data indicate that cells with MSC-like phenotype infiltrate into the tumor stroma and play an important role in tumor cell growth in vitro and in vivo. Thus, we suggest that targeting BT-MSCs could be a possible strategy for treating glioblastoma patients.

Original languageEnglish (US)
Pages (from-to)1110-1123
Number of pages14
JournalSTEM CELLS
Volume32
Issue number5
DOIs
StatePublished - May 2014
Externally publishedYes

Keywords

  • Cell adhesion molecules
  • Cell biology
  • Cell culture
  • Cell migration
  • Cell surface markers
  • Glioma
  • Mesenchymal stem cells
  • Multipotential differentiation
  • Recruited cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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