A Functional Study of Notch Signaling in Brain Cancer Stem-like Cells

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults and confers a dismal prognosis. Despite intense effort, treatment remains a significant therapeutic challenge and new modalities are desperately needed. In recent years a population of cancer cells with neural stem cell (NSC)-like properties has been reported in GBM. It is hypothesized that these so- called brain cancer stem-like cells (bCSC) are involved in brain tumor initiation, progression and treatment resistance. The Notch signaling pathway is known to be important in maintaining an undifferentiated pool of normal NSC and in determination of cell fate. Several recent data implicate a functional role for Notch signaling in GBM cells and when considering its role in normal NSC, the Notch signaling pathway might be an appropriate target for bCSC directed GBM therapy. The aim of the present project was to establish and characterize GBM stem-like cell cultures from xenograft tumors originating from human primary GBM, and subsequently investigate the significance of Notch expression and activation in these cultures.