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Targeting interleukin 6 signaling suppresses glioma stem cell survival and tumor growth.

Publication ,  Journal Article
Wang, H; Lathia, JD; Wu, Q; Wang, J; Li, Z; Heddleston, JM; Eyler, CE; Elderbroom, J; Gallagher, J; Schuschu, J; MacSwords, J; Cao, Y ...
Published in: Stem Cells
October 2009

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 (IL6R alpha) and glycoprotein 130 (gp130). Targeting IL6R alpha 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 IL6R alpha 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.

Duke Scholars

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Published In

Stem Cells

DOI

EISSN

1549-4918

Publication Date

October 2009

Volume

27

Issue

10

Start / End Page

2393 / 2404

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Signal Transduction
  • STAT3 Transcription Factor
  • Receptors, Interleukin-6
  • RNA, Small Interfering
  • RNA Interference
  • Neoplastic Stem Cells
  • Mice, Nude
  • Mice
 

Citation

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Wang, H., Lathia, J. D., Wu, Q., Wang, J., Li, Z., Heddleston, J. M., … Rich, J. N. (2009). Targeting interleukin 6 signaling suppresses glioma stem cell survival and tumor growth. Stem Cells, 27(10), 2393–2404. https://doi.org/10.1002/stem.188
Wang, Hui, Justin D. Lathia, Qiulian Wu, Jialiang Wang, Zhizhong Li, John M. Heddleston, Christine E. Eyler, et al. “Targeting interleukin 6 signaling suppresses glioma stem cell survival and tumor growth.Stem Cells 27, no. 10 (October 2009): 2393–2404. https://doi.org/10.1002/stem.188.
Wang H, Lathia JD, Wu Q, Wang J, Li Z, Heddleston JM, et al. Targeting interleukin 6 signaling suppresses glioma stem cell survival and tumor growth. Stem Cells. 2009 Oct;27(10):2393–404.
Wang, Hui, et al. “Targeting interleukin 6 signaling suppresses glioma stem cell survival and tumor growth.Stem Cells, vol. 27, no. 10, Oct. 2009, pp. 2393–404. Pubmed, doi:10.1002/stem.188.
Wang H, Lathia JD, Wu Q, Wang J, Li Z, Heddleston JM, Eyler CE, Elderbroom J, Gallagher J, Schuschu J, MacSwords J, Cao Y, McLendon RE, Wang X-F, Hjelmeland AB, Rich JN. Targeting interleukin 6 signaling suppresses glioma stem cell survival and tumor growth. Stem Cells. 2009 Oct;27(10):2393–2404.
Journal cover image

Published In

Stem Cells

DOI

EISSN

1549-4918

Publication Date

October 2009

Volume

27

Issue

10

Start / End Page

2393 / 2404

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Signal Transduction
  • STAT3 Transcription Factor
  • Receptors, Interleukin-6
  • RNA, Small Interfering
  • RNA Interference
  • Neoplastic Stem Cells
  • Mice, Nude
  • Mice