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Molecular and Cellular Biochemistry

, Volume 412, Issue 1–2, pp 1–10 | Cite as

Malignant transformation of bone marrow stromal cells induced by the brain glioma niche in rats

  • Qiuping He
  • Xifeng Zou
  • Deyi Duan
  • Yujun Liu
  • Qunyuan XuEmail author
Article

Abstract

Normal human embryonic stem cells (hESCs) can develop neoplastic cancer stem cell (CSC) properties after coculture with transformed hESCs in vitro. In the present study, the influence of the tumor microenvironment on malignant transformation of bone marrow stromal cells (BMSCs) was studied after allografting a mixture of enhanced green fluorescent protein (EGFP)-labeled BMSCs and C6 glioma cells into the rat brain to understand the influence of the cellular environment, especially the tumor environment, on the transformation of grafted BMSCs in the rat brain. We performed intracerebral transplantation in the rat brain using EGFP-labeled BMSCs coinjected with C6 tumor cells. After transplantation, the EGFP-labeled cells were isolated from the tumor using fluorescence-activated cell sorting, and the characteristics of the recovered cells were investigated. Glioma-specific biomarkers of the sorted cells and the biological characteristics of the tumors were analyzed. The BMSCs isolated from the cografts were transformed into glioma CSCs, as indicated by the marked expression of the glioma marker GFAP in glioma cells, and of Nestin and CD133 in neural stem cells and CSCs, as well as rapid cell growth, decreased level of the tumor suppressor gene p53, increased level of the oncogene murine double minute gene 2 (MDM2), and recapitulation of glioma tissues in the brain. These data suggest that BMSCs can be transformed into CSCs, which can be further directed toward glioma formation under certain conditions, supporting the notion that the tumor microenvironment is involved in transforming normal BMSCs into glial CSCs.

Keywords

Bone marrow stromal cell Transformation Glioma Cancer stem cell C6 

Abbreviations

BMSC

Bone marrow stromal cells

CSC

Cancer stem cells

EGFP

Enhanced green fluorescent protein

FACS

Fluorescence-activated cell sorting

GFAP

Glial fibrillary acidic protein

Notes

Acknowledgments

This study was supported by a grant from the National Basic Research Program of China (No. 2007CB947704).

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Qiuping He
    • 1
    • 2
  • Xifeng Zou
    • 1
    • 2
    • 3
  • Deyi Duan
    • 1
    • 2
  • Yujun Liu
    • 1
    • 2
  • Qunyuan Xu
    • 1
    • 2
    Email author
  1. 1.Beijing Institute for Brain Disorders, Beijing Centre for Neural Regeneration and Repair, Beijing Key Laboratory of Brain Major Disorders, Key Laboratory for Neurodegenerative Diseases of The Ministry of EducationCapital Medical UniversityBeijingChina
  2. 2.Department of NeurobiologyCapital Medical UniversityBeijingChina
  3. 3.Department of Neurosurgery, Xijing HospitalThe First Affiliated Hospital of the Fourth Military Medical UniversityXi’anChina

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