Telephone: +1-216-636-1667; Fax: +1-216-636-5454
Cancer Stem Cells
Version of Record online: 5 AUG 2009
Copyright © 2009 AlphaMed Press
Volume 27, Issue 10, pages 2393–2404, October 2009
How to Cite
Wang, H., Lathia, J. D., Wu, Q., Wang, J., Li, Z., Heddleston, J. M., Eyler, C. E., Elderbroom, J., Gallagher, J., Schuschu, J., MacSwords, J., Cao, Y., McLendon, R. E., Wang, X.-F., Hjelmeland, A. B. and Rich, J. N. (2009), Targeting Interleukin 6 Signaling Suppresses Glioma Stem Cell Survival and Tumor Growth. STEM CELLS, 27: 2393–2404. doi: 10.1002/stem.188
Author contributions: H.W.: Financial support conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; J.D.L.: Financial support, conception and design, collection and/or assembly of data; Q.W.: Collection and/or assembly of data; J.W.: Financial support, collection and/or assembly of data; Z.L.: Conception and design, collection and/or assembly of data; J.M.H.: Collection and/or assembly of data; C.E.E.: Collection and/or assembly of data; J.E.: Collection and/or assembly of data; J.G.: Collection and/or assembly of data; J.S.: Collection and/or assembly of data; J.M.: Collection and/or assembly of data; Y.C.: Financial support, collection and/or assembly of data; R.E.M.: Provision of study materials or patients, collection and/or assembly of data; X.-F.W.: Financial support, conception and design; A.B.H.: Financial support, conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; J.N.R.: Financial support, conception and design, manuscript writing, final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLS EXPRESS August 5, 2009.
- Issue online: 13 OCT 2009
- Version of Record online: 5 AUG 2009
- Accepted manuscript online: 5 AUG 2009 12:00AM EST
- Manuscript Accepted: 24 JUL 2009
- Manuscript Received: 2 APR 2009
- Childhood Brain Tumor Foundation
- Pediatric Brain Tumor Foundation of the United States
- Accelerate Brain Cancer Cure
- Alexander and Margaret Stewart Trust
- Brain Tumor Society
- Goldhirsh Foundation
- Sidney Kimmel Foundation
- Damon Runyon Cancer Research Foundation
- Southeastern Brain Tumor Foundation
- American Brain Tumor Association
- NIH grants. Grant Numbers: NS047409, NS054276, CA129958, CA116659, CA122998
- The Duke University Brain Tumor Tissue Bank
- Duke University Brain Cancer SPORE
- 1Central Brain Tumor Registry of the United States, Statistical Report: Primary Brain Tumors in the United States, 1998–2002. Published by the Central Brain Tumor Registry of the United States, 2005.
- 2Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci USA 2003; 100: 15178–15183., , et al.
- 3Identification of human brain tumour initiating cells. Nature 2004; 432: 396–401., , et al.
- 4Molecular and cell biology of brain tumor stem cells: lessons from neural progenitor/stem cells. Neurosurg Focus 2008; 24: E25., .
- 5GSCs promote radioresistance by preferential activation of the DNA damage response. Nature 2006; 444: 756–760., , et al.
- 6Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Res 2006; 66: 7843–7848., , et al.
- 7Targeting cancer stem cells through L1CAM suppresses glioma growth. Cancer Res 2008; 68: 6043–6048., , et al.
- 8Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell 2009; 15: 501–513., , et al.
- 9Olig2-regulated lineage-restricted pathway controls replication competence in neural stem cells and malignant glioma. Neuron 2007; 53: 503–517., , et al.
- 10Chemotherapy resistance of glioblastoma stem cells. Cell Death Differ 2006; 13: 1238–1241., , et al.
- 11Cancer stem cell analysis and clinical outcome in patients with glioblastoma multiforme. Clin Cancer Res 2008; 14: 8205–8212., , et al.
- 12Stem cell marker CD133 affects clinical outcome in glioma patients. Clin Cancer Res 2008; 14: 123–129., , et al.
- 13Interleukin-6: from basic science to medicine: 40 years in immunology. Annu Rev Immunol 2005; 23: 1–21..
- 14The role of IL6 and STAT3 in inflammation and cancer. Eur J Cancer 2005; 41: 2502–2012., , .
- 15Fas engagement increases expression of interleukin-6 in human glioma cells. J Neurooncol 2002; 56: 13–19., , et al.
- 16Interleukin-6 gene amplification and shortened survival in glioblastoma patients. Br J Cancer 2007; 96: 474–476., , et al.
- 17IL6 is required for glioma development in a mouse model. Oncogene 2004; 23: 3308–3316., , et al.
- 18Proliferation of astrocytes in vitro in response to cytokines. J Immunol 1990; 144: 129–135., , et al.
- 19Interleukin-6 (IL6) does not change the expression of Bcl-2 protein in the prevention of cisplatin-induced apoptosis in ovarian cancer cell lines. J Obstet Gynaecol Res 1999; 25: 23–27., , et al.
- 20Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis. Genes Dev 2007; 21: 1714–1719., , .
- 21Autocrine production of interleukin 6 causes multidrug resistance in breast cancer cells. Cancer Res 2001; 61: 8851–8858., , et al.
- 22Interleukin-6 enhances motility of breast carcinoma cells. EXS 1991; 59: 178–193., .
- 23IL6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland. J Clin Invest 2007; 117: 3988–4002., , et al.
- 24Inhibition of constitutively active Stat3 suppresses proliferation and induces apoptosis in glioblastoma multiforme cells. Oncogene 2002; 21: 8404–8013., , et al.
- 25Analysis of the activation status of Akt, NFkappaB, and Stat3 in human diffuse gliomas. Lab Invest 2004; 84: 941–951., , et al.
- 26Knockdown of STAT3 expression by RNAi induces apoptosis in astrocytoma cells. BMC Cancer 2003; 3: 23., , et al.
- 27JSI-124 inhibits glioblastoma multiforme cell proliferation through G(2)/M cell cycle arrest and apoptosis augment. Cancer Biol Ther 2008; 7: 1243–1249., , et al.
- 28STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells. EMBO J 1999; 18: 4261–4269., , et al.
- 29Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3. Genes Dev 1998; 12: 2048–2060., , et al.
- 30Direct orthotopic transplantation of fresh surgical specimen preserves CD133+ tumor cells in clinically relevant mouse models of medulloblastoma and glioma. Stem Cells 2008; 26: 1414–1424., , et al.
- 31Stattic: a small-molecule inhibitor of STAT3 activation and dimerization. Chem Biol 2006; 13: 1235–1242., , et al.
- 32Hypoxia—a key regulatory factor in tumour growth. Nat Rev Cancer 2002; 2: 38–47..
- 33Interleukin-6 induces transcriptional activation of vascular endothelial growth factor (VEGF) in astrocytes in vivo and regulates VEGF promoter activity in glioblastoma cells via direct interaction between STAT3 and Sp1. Int J Cancer 2005; 115: 202–213., , et al.
- 34Targeted anti-interleukin-6 monoclonal antibody therapy for cancer: a review of the rationale and clinical evidence. Clin Cancer Res 2003; 9: 4653–4665., , et al.
- 35Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 2007; 25: 4722–4729., , et al.