| Autor: |
Hui Wang, Lathia, Justin D., Qiulian Wu, Jialiang Wang, Zhizhong Li, Heddleston, John M., Eyler, Christine E., Elderbroom, Jennifer, Gallagher, Joseph, Schuschu, Jesse, MacSwords, Jennifer, Yiting Cao, McLendon, Roger E., Xiao-Fan Wang, Hjelmeland, Anita B., Rich, Jeremy N. |
| Předmět: |
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| Zdroj: |
Stem Cells; Oct2009, Vol. 27 Issue 10, p2393-2404, 12p, 3 Color Photographs, 6 Graphs |
| Abstrakt: |
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 (IL6Ra) and glycoprotein 130 (gpl30). Targeting IL6Ra or IL6 ligand expression in GSCs with the use of short hairpin RNAs (shRNAs) significantly reduces growth and neuro- sphere 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 STA 13 is a downstream mediator of prosurvival IL6 signals in GSCs. Targeting of IL6Ra or IL6 expression in GSCs increases the survival of mice bearing intracranial human ½liorna 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. Stem Cells 2009;27.-2393-2404 [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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