TLX activates MMP-2, promotes self-renewal of tumor spheres in neuroblastoma and correlates with poor patient survival.

摘要: Nuclear orphan receptor TLX (Drosophila tailless homolog) is essential for the maintenance of neural stem/progenitor cell self-renewal, but its role in neuroblastoma (NB) not well understood. Here, we show that formation tumor spheres three different NB lines, when grown stem media. We demonstrate knock down IMR-32 cells diminishes sphere-forming capacity. In spheres, coexpressed with progenitor markers Nestin, CD133 and Oct-4. addition, migratory CD15 matrix metalloproteinase-2 (MMP-2) xenografts primary from patients. Subsequently, effect on proliferative, invasive properties cells. attribute this to recruitment both MMP-2 Oct-4 gene promoters, which resulted respective activation. support our findings, found expression was high patient tissues compared normal peripheral nervous system tissues. Further, Kaplan–Meier estimator indicated a negative correlation between survival 88 Therefore, results point at being crucial player progression NB, by promoting self-renewal tumor-initiating altering their properties.