| Literature DB >> 25047528 |
Andreas Herrmann1, Gregory Cherryholmes1, Anne Schroeder2, Jillian Phallen3, Darya Alizadeh4, Hong Xin1, Tianyi Wang1, Heehyoung Lee1, Christoph Lahtz1, Piotr Swiderski2, Brian Armstrong5, Claudia Kowolik2, Gary L Gallia3, Michael Lim3, Christine Brown6, Behnam Badie4, Stephen Forman6, Marcin Kortylewski1, Richard Jove2, Hua Yu7.
Abstract
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. Cancer Res; 74(18); 5218-28. ©2014 AACR. ©2014 American Association for Cancer Research.Entities:
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Year: 2014 PMID： 25047528 PMCID： PMC4167470 DOI： 10.1158/0008-5472.CAN-14-1151
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701