Document Detail


Antitumor effect of humanized anti-interleukin-6 receptor antibody (tocilizumab) on glioma cell proliferation. Laboratory investigation.
MedLine Citation:
PMID:  19326989     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECT: Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates diverse physiological functions, including cell proliferation and survival. Recent studies have shown that IL-6 expression is often elevated in response to several types of glioma. Although IL-6 is said to play an important role in glioma, the involvement of IL-6 signaling has been quite controversial. The aim of this study was to evaluate the involvement of IL-6 signaling in glioma and the inhibitory effect of IL-6 signaling on glioma tumor proliferation. METHODS: The expression of IL-6 receptors (IL-6Rs) was evaluated in glioma tissues by means of immunohistochemical analysis, and the involvement of IL-6 signaling in glioblastoma multiforme (GBM) U87MG cell proliferation was also determined. In addition, to examine the inhibitory effect of IL-6 signaling on glioma cell proliferation, the authors investigated the effects of tocilizumab, the humanized anti-human IL-6R antibody in U87MG cells. RESULTS: Increased immunoreactivity for IL-6R was predominantly found in the cytoplasm of endothelial cells in all GBM samples. Inhibition of IL-6 signaling by both IL-6- and IL-6R-specific small interfering RNA and AG490, a specific inhibitor of JAK2 phosphorylation, suppressed glioma cell proliferation. Furthermore, tocilizumab, a clinically developed humanized anti-human IL-6R antibody, exerted an antiproliferative effect on cells from the GBM cell line U87MG via the IL-6R-dependent JAK-STAT3 pathway. CONCLUSIONS: The IL-6 signaling pathway plays an important role in glioma cell proliferation, and tocilizumab exerts an antitumor effect in U87MG glioma cells. These results may bring new insight into the molecular pathogenesis of glioma and may lead to a new therapeutic intervention.
Authors:
Mareina Kudo; Hirofumi Jono; Satoru Shinriki; Shigetoshi Yano; Hideo Nakamura; Keishi Makino; Takuichiro Hide; Daisuke Muta; Mitsuharu Ueda; Kazutoshi Ota; Yukio Ando; Jun-Ichi Kuratsu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neurosurgery     Volume:  111     ISSN:  0022-3085     ISO Abbreviation:  J. Neurosurg.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-08-03     Completed Date:  2009-09-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0253357     Medline TA:  J Neurosurg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  219-25     Citation Subset:  AIM; IM    
Affiliation:
Department of Neurosurgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
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MeSH Terms
Descriptor/Qualifier:
Antibodies, Monoclonal / pharmacology*
Blotting, Western
Cell Division / drug effects
Glioma / chemistry,  pathology*
Humans
Immunohistochemistry
Interleukin-6 / physiology*
Polymerase Chain Reaction
Receptors, Interleukin-6 / analysis,  immunology
Signal Transduction / physiology
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Interleukin-6; 0/Receptors, Interleukin-6; 0/tocilizumab

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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