Targeting Interleukin 6 Signaling Suppresses Glioma Stem Cell Survival and Tumor Growth (original) (raw)

Journal Article

Hui Wang ,

Departments of Pharmacology and Cancer Biology, Duke University Medical Center

, Durham, North Carolina,

USA

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Justin D. Lathia ,

Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic

, Cleveland, Ohio,

USA

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Qiulian Wu ,

Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic

, Cleveland, Ohio,

USA

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Jialiang Wang ,

Departments ofSurgery, and Duke University Medical Center

, Durham, North Carolina,

USA

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Zhizhong Li ,

Departments of Pharmacology and Cancer Biology, Duke University Medical Center

, Durham, North Carolina,

USA

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John M. Heddleston ,

Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic

, Cleveland, Ohio,

USA

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Christine E. Eyler ,

Departments of Pharmacology and Cancer Biology, Duke University Medical Center

, Durham, North Carolina,

USA

Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic

, Cleveland, Ohio,

USA

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Jennifer Elderbroom ,

Departments of Pharmacology and Cancer Biology, Duke University Medical Center

, Durham, North Carolina,

USA

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Joseph Gallagher ,

Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic

, Cleveland, Ohio,

USA

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Jesse Schuschu

Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic

, Cleveland, Ohio,

USA

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... Show more

Published:

05 August 2009

Cite

Hui Wang, Justin D. Lathia, Qiulian Wu, Jialiang Wang, Zhizhong Li, John M. Heddleston, Christine E. Eyler, Jennifer Elderbroom, Joseph Gallagher, Jesse Schuschu, Jennifer MacSwords, Yiting Cao, Roger E. McLendon, Xiao-Fan Wang, Anita B. Hjelmeland, Jeremy N. Rich, Targeting Interleukin 6 Signaling Suppresses Glioma Stem Cell Survival and Tumor Growth, Stem Cells, Volume 27, Issue 10, October 2009, Pages 2393–2404, https://doi.org/10.1002/stem.188
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Abstract

Glioblastomas are the most common and most lethal primary brain tumor. Recent studies implicate an important role for a restricted population of neoplastic cells (glioma stem cells (GSCs)) in glioma maintenance and recurrence. We now demonstrate that GSCs preferentially express two interleukin 6 (IL6) receptors: IL6 receptor alpha (IL6Rα) and glycoprotein 130 (gp130). Targeting IL6Rα or IL6 ligand expression in GSCs with the use of short hairpin RNAs (shRNAs) significantly reduces growth and neurosphere formation capacity while increasing apoptosis. Perturbation of IL6 signaling in GSCs attenuates signal transducers and activators of transcription three (STAT3) activation, and small molecule inhibitors of STAT3 potently induce GSC apoptosis. These data indicate that STAT3 is a downstream mediator of prosurvival IL6 signals in GSCs. Targeting of IL6Rα or IL6 expression in GSCs increases the survival of mice bearing intracranial human glioma xenografts. IL6 is clinically significant because elevated IL6 ligand and receptor expression are associated with poor glioma patient survival. The potential utility of anti-IL6 therapies is demonstrated by decreased growth of subcutaneous human GSC-derived xenografts treated with IL6 antibody. Together, our data indicate that IL6 signaling contributes to glioma malignancy through the promotion of GSC growth and survival, and that targeting IL6 may offer benefit for glioma patients.

Copyright © 2009 AlphaMed Press

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