Leptin and Notch Signaling Cooperate in Sustaining Glioblastoma Multiforme Progression

摘要: Glioblastoma multiforme (GBM) is the most malignant form of glioma, which represents one commonly occurring tumors central nervous system. Despite continuous development new clinical therapies against this malignancy, it still remains a deadly disease with very poor prognosis. Here, we demonstrated existence biologically active interaction between leptin and Notch signaling pathways that sustains GBM progression. We found expression its receptors was significantly higher in human glioblastoma cells, U-87 MG T98G, than normal glial cell line, SVG p12, activation induced growth motility cells. Interestingly, flow cytometry real-time RT-PCR assays revealed grown as neurospheres, displayed stem cell-like properties (CD133+) along an enhanced receptors. Leptin treatment increased neurosphere forming efficiency, self-renewal capacity, mRNA levels stemness markers CD133, Nestin, SOX2, GFAP. Mechanistically, evidenced leptin-mediated upregulation 1 receptor downstream effectors target molecules. Leptin-induced effects on T98G cells were abrogated by selective antagonist, peptide LDFI (Leu-Asp-Phe-Ile), well specific inhibitor, GSI (Gamma Secretase Inhibitor) presence dominant-negative mastermind-like-1. Overall, these findings demonstrate, for first time, functional GBM, highlighting leptin/Notch crosstalk potential novel therapeutic treatment.