TLR9 Is Critical for Glioma Stem Cell Maintenance and Targeting

被引：59

作者：

Herrmann, Andreas ^{[1
]}

Cherryholmes, Gregory ^{[1
]}

Schroeder, Anne ^{[2
]}

Phallen, Jillian ^{[3
]}

Alizadeh, Darya ^{[4
]}

Xin, Hong ^{[1
]}

Wang, Tianyi ^{[1
]}

Lee, Heehyoung ^{[1
]}

Lahtz, Christoph ^{[1
]}

Swiderski, Piotr ^{[2
]}

Armstrong, Brian ^{[5
]}

Kowolik, Claudia ^{[2
]}

Gallia, Gary L. ^{[3
]}

Lim, Michael ^{[3
]}

Brown, Christine ^{[6
]}

Badie, Behnam ^{[4
]}

Forman, Stephen ^{[6
]}

Kortylewski, Marcin ^{[1
]}

Jove, Richard ^{[2
]}

Yu, Hua ^{[1
,7
]}

机构：

[1] City Hope Med Ctr, Beckman Res Inst, Dept Canc Immunotherapeut & Tumor Immunol, Duarte, CA USA

[2] City Hope Med Ctr, Beckman Res Inst, Dept Mol Med, Duarte, CA USA

[3] Johns Hopkins Univ, Sch Med, Dept Neurosurg, Sidney Kimmel Canc Ctr, Baltimore, MD 21205 USA

[4] City Hope Med Ctr, Div Neurosurg, Duarte, CA USA

[5] City Hope Med Ctr, Beckman Res Inst, Dept Neurosci, Duarte, CA USA

[6] City Hope Med Ctr, Dept Hematol & Hematopoiet Cell Transplant, Duarte, CA USA

[7] Ctr Translat Med, Shanghai, Peoples R China

来源：

CANCER RESEARCH | 2014年 / 74卷 / 18期

关键词：

TOLL-LIKE RECEPTORS; CANCER-THERAPY; T-CELLS; IN-VIVO; TUMOR MICROENVIRONMENT; IMMUNE-RESPONSES; INNATE IMMUNITY; SELF-RENEWAL; BRAIN-TUMORS; STAT3;

D O I：

10.1158/0008-5472.CAN-14-1151

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Understanding supports for cancer stem-like cells in malignant glioma may suggest therapeutic strategies for their elimination. Here, we show that the Toll-like receptor TLR9 is elevated in glioma stem-like cells (GSC) in which it contributes to glioma growth. TLR9 overexpression is regulated by STAT3, which is required for GSC maintenance. Stimulation of TLR9 with a CpG ligand (CpG ODN) promoted GSC growth, whereas silencing TLR9 expression abrogated GSC development. CpG-ODN treatment induced Frizzled4-dependent activation of JAK2, thereby activating STAT3. Targeted delivery of siRNA into GSC was achieved via TLR9 using CpG-siRNA conjugates. Through local or systemic treatment, administration of CpG-Stat3 siRNA to silence STAT3 in vivo reduced GSC along with glioma growth. Our findings identify TLR9 as a functional marker for GSC and a target for the delivery of efficacious therapeutics for glioma treatment. (C)2014 AACR.

引用

页码：5218 / 5228

页数：11

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