Human glioma stem-like cells induce malignant transformation of bone marrow mesenchymal stem cells by activating TERT expression

Yaodong Zhao, Jinsheng Chen, Xingliang Dai, Honghua Cai, Xiaoyan Ji, Yujing Sheng, Hairui Liu, Lin Yang, Yanming Chen, Dengguo Xi, Minfeng Sheng, Yanping Xue, Jia Shi, Jiachi Liu, Xiaonan Li, Jun Dong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

We investigated whether glioma stem-like cells (GSCs) malignantly transformed bone marrow mesenchymal stem cells (tBMSCs) in the tumor microenvironment. Transplantation of enhanced green fluorescence protein (EGFP)-labeled BMSCs into irradiated athymic nude mice was followed by intracranial injection of red fluorescent protein-expressing glioma stem-like cells (SU3-RFP-GSCs). Singly cloned EGFP-BMSCs, harvested from the intracranial tumors showed TERT overexpression, high proliferation, colony formation and invasiveness in Transwell matrigel assays. Transfection of normal BMSCs with TERT (TERT-BMSCs) enhanced proliferation, colony formation and invasiveness, though these characteristics remained lower than in tBMSCs. The tBMSCs and TERT-BMSCs showed high surface expression of CD44, CD105, CD29 and CD90 and an absence of CD31, CD34, CD45, and CD11b, as in normal BMSCs. Alizarin red S and oil red O staining confirmed tBMSCs and TERTBMSCs transdifferentiated into osteocytes and adipocytes, respectively. When normal BMSCs were indirectly co-cultured in medium from SU3-RFP-GSCs, they exhibited increased growth and proliferation, suggesting paracrine factors from GSCs induced their malignant transformation. Tumorigenicity assays in athymic nude mice showed that transplanted tBMSCs and TERT-BMSCs generated 100% and 20% subcutaneous tumors, respectively, while normal BMSCs generated no tumors. GSCs thus induce malignant transformation of BMSCs by activating TERT expression in BMSCs.

Original languageEnglish (US)
Pages (from-to)104418-104429
Number of pages12
JournalOncotarget
Volume8
Issue number61
DOIs
StatePublished - 2017

Keywords

  • Bone marrow mesenchymal stem cells
  • Glioma stem-like cells
  • Malignant transformation
  • TERT

ASJC Scopus subject areas

  • Oncology

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