Abstract
Abstract Glioblastoma multiforme (GBM) is the most common and deadly form of brain cancer. Despite intensive research the median survival of GBM remains at 1 year, with less than 10 % of patients surviving over 5 years. Our analysis of fresh GBM, secondary GBM, high grade astrocytoma, oligodendroglioma, normal brain and normal human astrocytes showed increased expression of 19 novel protein kinases in GBM and targets previously associated with gliomagenesis (e.g. EGFR or PDGF). Two of these kinases which are mainly expressed in hematopoietic cells were the cytoplasmic kinases SYK and LYN. We confirmed the overexpression in GBM tumours and cell lines through western blot and immunohistochemistry analysis. More importantly, SYK expression was derived from the GBM tumours and not from infiltrating leukocytes as shown through colocalization with GFAP, and not with CD45. SYK was found strongly activated at the membrane after EGF and treatment with three specific small molecule inhibitors and siRNA targeting SYK strongly blocked proliferation and migration of GBM cells. This was confirmed through wtSYK and kinase dead SYK overexpression. In addition, SYK phosphorylation was found to be cell cycle regulated after synchronization. Due to our preliminary results we will test the therapeutic potential of SYK inhibitors and epistatic kinase interactions on our xenograft model measuring the efficacy of therapeutics crossing the blood brain barrier with the ultimate goal of discovering alternative treatments for GBM. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1240. doi:1538-7445.AM2012-1240
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