PMID- 19658188
OWN - NLM
STAT- MEDLINE
DCOM- 20100217
LR  - 20220223
IS  - 1549-4918 (Electronic)
IS  - 1066-5099 (Print)
IS  - 1066-5099 (Linking)
VI  - 27
IP  - 10
DP  - 2009 Oct
TI  - Targeting interleukin 6 signaling suppresses glioma stem cell survival and tumor 
      growth.
PG  - 2393-404
LID - 10.1002/stem.188 [doi]
AB  - 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.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Pharmacology, Duke University Medical Center, Durham, North 
      Carolina, USA.
FAU - Lathia, Justin D
AU  - Lathia JD
FAU - Wu, Qiulian
AU  - Wu Q
FAU - Wang, Jialiang
AU  - Wang J
FAU - Li, Zhizhong
AU  - Li Z
FAU - Heddleston, John M
AU  - Heddleston JM
FAU - Eyler, Christine E
AU  - Eyler CE
FAU - Elderbroom, Jennifer
AU  - Elderbroom J
FAU - Gallagher, Joseph
AU  - Gallagher J
FAU - Schuschu, Jesse
AU  - Schuschu J
FAU - MacSwords, Jennifer
AU  - MacSwords J
FAU - Cao, Yiting
AU  - Cao Y
FAU - McLendon, Roger E
AU  - McLendon RE
FAU - Wang, Xiao-Fan
AU  - Wang XF
FAU - Hjelmeland, Anita B
AU  - Hjelmeland AB
FAU - Rich, Jeremy N
AU  - Rich JN
LA  - eng
GR  - R01 CA116659/CA/NCI NIH HHS/United States
GR  - R01 NS054276-03/NS/NINDS NIH HHS/United States
GR  - R01 CA116659-05/CA/NCI NIH HHS/United States
GR  - CA122998/CA/NCI NIH HHS/United States
GR  - CA129958/CA/NCI NIH HHS/United States
GR  - R01 CA116659-04/CA/NCI NIH HHS/United States
GR  - CA116659/CA/NCI NIH HHS/United States
GR  - R01 CA122998/CA/NCI NIH HHS/United States
GR  - K02 NS047409-04/NS/NINDS NIH HHS/United States
GR  - R01 CA129958-02/CA/NCI NIH HHS/United States
GR  - R01 CA129958/CA/NCI NIH HHS/United States
GR  - R01 CA122998-04/CA/NCI NIH HHS/United States
GR  - R01 CA122998-03/CA/NCI NIH HHS/United States
GR  - NS054276/NS/NINDS NIH HHS/United States
GR  - K02 NS047409/NS/NINDS NIH HHS/United States
GR  - NS047409/NS/NINDS NIH HHS/United States
GR  - R01 NS054276/NS/NINDS NIH HHS/United States
GR  - R01 CA129958-01A1/CA/NCI NIH HHS/United States
GR  - R01 NS054276-04/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - 0 (Growth Inhibitors)
RN  - 0 (Interleukin-6)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Interleukin-6)
RN  - 0 (STAT3 Transcription Factor)
RN  - 133483-10-0 (Cytokine Receptor gp130)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics
MH  - Brain Neoplasms/*drug therapy/genetics/immunology
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects/genetics/immunology
MH  - Cytokine Receptor gp130/drug effects/genetics/metabolism
MH  - Glioma/*drug therapy/genetics/immunology
MH  - Graft Survival/drug effects/physiology
MH  - Growth Inhibitors/pharmacology
MH  - Humans
MH  - Interleukin-6/*antagonists & inhibitors/metabolism
MH  - Mice
MH  - Mice, Nude
MH  - Neoplastic Stem Cells/*drug effects/immunology/metabolism
MH  - RNA Interference/physiology
MH  - RNA, Small Interfering/pharmacology
MH  - Receptors, Interleukin-6/drug effects/genetics/metabolism
MH  - STAT3 Transcription Factor/metabolism
MH  - Signal Transduction/drug effects/genetics/immunology
MH  - Transplantation, Heterologous
MH  - Tumor Cells, Cultured
PMC - PMC2825688
MID - NIHMS165168
COIS- Disclaimers: The authors have no potential conflicts of interest.
EDAT- 2009/08/07 09:00
MHDA- 2010/02/18 06:00
PMCR- 2010/10/01
CRDT- 2009/08/07 09:00
PHST- 2009/08/07 09:00 [entrez]
PHST- 2009/08/07 09:00 [pubmed]
PHST- 2010/02/18 06:00 [medline]
PHST- 2010/10/01 00:00 [pmc-release]
AID - 10.1002/stem.188 [doi]
PST - ppublish
SO  - Stem Cells. 2009 Oct;27(10):2393-404. doi: 10.1002/stem.188.