Investigation of integrin expression in cancer stem cells isolated from glioblastoma patients

Glioblastoma multiforme (GBM) is the most common primary brain tumor, which despite combined treatment modalities recurs, and is invariably fatal within a year of diagnosis. The recent characterization of stem cell-like populations in this tumor (glioma stem cells, “GSCs”), shown to be responsible for GBM initiation and progression, has prompted the study of new therapies for GBM to specifically target GSCs. Here we have focused our studies on integrins, which are heterodimeric transmembrane surface proteins that, when activated, have been shown to signal through several GBM-relevant pathways, including proliferation, motility, cytoskeleton organization, survival and angiogenesis pathways. Accordingly, these molecules have attracted a lot of interest since potential effects of anti-integrin strategies in GBM therapeutics might be threefold: anti-angiogenesis, anti-invasion and anti-tumor. Here we investigated integrins’ expression in GSCs, isolated and derived from patients’ biopsies and cultured in monolayer and a serum free medium. The expression of different integrins was examined by PCR, FACS and immunocytochemistry. Our results showed that GSCs express αvβ3, αvβ5 and α5β1 integrins, the expression levels being higher expression than tissue control. Our aim is now to modulate integrin signaling by means of downregulation/upregulation of respectively oncogenic/tumor suppressor miRNAs.