TY - JOUR TI - Caspase-8 contributes to angiogenesis and chemotherapy resistance in glioblastoma AU - Fianco, Giulia AU - Mongiardi, Maria Patrizia AU - Levi, Andrea AU - De Luca, Teresa AU - Desideri, Marianna AU - Trisciuoglio, Daniela AU - Del Bufalo, Donatella AU - Cinà, Irene AU - Di Benedetto, Anna AU - Mottolese, Marcella AU - Gentile, Antonietta AU - Centonze, Diego AU - Ferrè, Fabrizio AU - Barilà, Daniela A2 - Cooper, Jonathan A VL - 6 PY - 2017 DA - 2017/06/08 SP - e22593 C1 - eLife 2017;6:e22593 DO - 10.7554/eLife.22593 UR - https://doi.org/10.7554/eLife.22593 AB - Caspase-8 is a key player in extrinsic apoptosis and its activity is often downregulated in cancer. However, human Caspase-8 expression is retained in some tumors, including glioblastoma (GBM), suggesting that it may support cancer growth in these contexts. GBM, the most aggressive of the gliomas, is characterized by extensive angiogenesis and by an inflammatory microenvironment that support its development and resistance to therapies. We have recently shown that Caspase-8 sustains neoplastic transformation in vitro in human GBM cell lines. Here, we demonstrate that Caspase-8, through activation of NF-kB, enhances the expression and secretion of VEGF, IL-6, IL-8, IL-1beta and MCP-1, leading to neovascularization and increased resistance to Temozolomide. Importantly, the bioinformatics analysis of microarray gene expression data derived from a set of high-grade human gliomas, shows that high Caspase-8 expression levels correlate with a worse prognosis. KW - mouse KW - cell death KW - cell proliferation KW - signal transduction KW - cancer KW - angiogenesis JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -