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KMID : 0613820190290050530
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Journal of Life Science
2019 Volume.29 No. 5 p.530 ~ p.536
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Different Cytokine Dependency of Proneural to Mesenchymal Glioma Stem Cell Transition in Tumor Microenvironments
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Lee Seon-Yong
Kim Hyung-Gee
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Abstract
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Glioblastoma (GBM) is the most incurable brain cancer derived from the transformed glial cells. Standard anti-GBM treatment, including surgery and chemoradiotherapy, does not ensure good prognosis for the patients with GBM, because successful therapy is often impeded by presence of glioma stem cells (GSCs). GSCs, which is generally divided into proneural (PN) and mesenchymal (MES) subtype, are understood as subpopulation of cancer cells responsible for GBM initiation, progression and recurrence after standard treatments. In the present study, we demonstrate that PN subtype GSCs differentially transit to MES subtype GSCs by specific cytokines. The expression of CD44, a marker of MES subtype GSCs, was observed when GSC11 PN subtype GSCs were exposed to tumor necrosis factor alpha (TNF-α) cytokine and GSC23 PN subtype GSCs were treated to transforming growth factor beta 1 (TGF-β1) cytokine. Ivy glioblastoma atlas project (Ivy GAP) bioinformatics database showed that TNF-α and TGF-β1 were highly expressed in necrotic region and perivascular region, respectively. In addition, TNF-α signaling was relatively upregulated in necrotic region, while TGF-β signaling was increased in perivascular region. Taken together, our observations suggest that MES subtype GSCs can be derived from various PN subtype GSCs by multimodal cytokine stimuli provided by neighboring tumor microenvironment.
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KEYWORD
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Glioma stem cell, PN-to-MES transition, TGF-β1, TNF-α, Tumor microenvironments
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