Targeting Self-Renewal in High-Grade Brain Tumors Leads to Loss of Brain Tumor Stem Cells and Prolonged Survival

摘要: Cancer stem cells (CSCs) have been suggested as potential therapeutic targets for treating malignant tumors, but the in vivo supporting evidence is still missing. Using a GFP reporter driven by promoter of nuclear receptor tailless (Tlx), we demonstrate that Tlx(+) primary brain tumors are mostly quiescent. Lineage tracing demonstrates single can self-renew and generate Tlx(-) tumor suggesting they (BTSCs). After introducing BTSC-specific knock-out Tlx gene mouse observed loss self-renewal BTSCs prolongation animal survival, accompanied induction essential signaling pathways mediating cell-cycle arrest, cell death, neural differentiation. Our study feasibility targeting glioblastomas indicates suitability targets, thereby CSC hypothesis.