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., Levi, A., De Luca, T., 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

FIANCO, GIULIA;GENTILE, ANTONIETTA;CENTONZE, DIEGO;BARILA', DANIELA
2017-06-08

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.
8-giu-2017
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/18 - GENETICA
Settore MED/26 - NEUROLOGIA
English
Con Impact Factor ISI
angiogenesis; cancer; cancer biology; cell biology; cell death; cell proliferation; human; mouse; signal transduction
https://elifesciences.org/articles/22593
Fianco, G., Mongiardi, M., Levi, A., De Luca, T., 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, G; Mongiardi, M; Levi, A; De Luca, T; Desideri, M; Trisciuoglio, D; Del Bufalo, D; Cinà, I; Di Benedetto, A; Mottolese, M; Gentile, A; Centonze, D; Ferrè, F; Barila', D
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/185017
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