TLR9 is Critical for Glioma Stem Cell Maintenance and Targeting
Menée in vitro et in vivo, cette étude met en évidence le rôle joué par la surexpression du récepteur TLR9 dans les cellules souches de gliome
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) where it contributes to glioma growth. TLR9 overexpression is regulated by STAT3 which was 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.