Caspase-8 contributes to angiogenesis and chemotherapy resistance in glioblastoma

Giulia Fianco, Maria Patrizia Mongiardi, Andrea Levi, Teresa De Luca, Marianna Desideri, Daniela Trisciuoglio, Donatella Del Bufalo, Irene Cinà, Anna Di Benedetto, Marcella Mottolese, Antonietta Gentile, Diego Centonze, Fabrizio Ferrè, Daniela Barilà

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article numbere22593
JournaleLife
Volume6
DOIs
Publication statusPublished - Jun 8 2017

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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  • Cite this

    Fianco, G., Mongiardi, M. P., Levi, A., Luca, T. D., Desideri, M., Trisciuoglio, D., Bufalo, D. D., Cinà, I., Benedetto, A. D., Mottolese, M., Gentile, A., Centonze, D., Ferrè, F., & Barilà, D. (2017). Caspase-8 contributes to angiogenesis and chemotherapy resistance in glioblastoma. eLife, 6, [e22593]. https://doi.org/10.7554/eLife.22593