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.

Fianco, G., Mongiardi, M.P., Levi, A., Luca, T.D., Desideri, M., Trisciuoglio, D., et al. (2017). Caspase-8 contributes to angiogenesis and chemotherapy resistance in glioblastoma. ELIFE, 6, 1-16 [10.7554/eLife.22593].

Caspase-8 contributes to angiogenesis and chemotherapy resistance in glioblastoma

Ferrè, Fabrizio;
2017

Abstract

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.
2017
Fianco, G., Mongiardi, M.P., Levi, A., Luca, T.D., Desideri, M., Trisciuoglio, D., et al. (2017). Caspase-8 contributes to angiogenesis and chemotherapy resistance in glioblastoma. ELIFE, 6, 1-16 [10.7554/eLife.22593].
Fianco, Giulia; Mongiardi, Maria Patrizia; Levi, Andrea; Luca, Teresa De; Desideri, Marianna; Trisciuoglio, Daniela; Bufalo, Donatella Del; Cinã , Ire...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/615382
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