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

9 Citations (Scopus)

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

Fingerprint

Chemotherapy
Caspase 8
Glioblastoma
Drug Therapy
temozolomide
Glioma
Neoplasms
NF-kappa B
Microarray Analysis
Bioinformatics
Microarrays
Computational Biology
Interleukin-8
Gene expression
Vascular Endothelial Growth Factor A
Tumors
Interleukin-6
Down-Regulation
Chemical activation
Cells

ASJC Scopus subject areas

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

Cite this

Caspase-8 contributes to angiogenesis and chemotherapy resistance in glioblastoma. / Fianco, Giulia; Mongiardi, Maria Patrizia; Levi, Andrea; Luca, Teresa De; Desideri, Marianna; Trisciuoglio, Daniela; Bufalo, Donatella Del; Cinà, Irene; Benedetto, Anna Di; Mottolese, Marcella; Gentile, Antonietta; Centonze, Diego; Ferrè, Fabrizio; Barilà, Daniela.

In: eLife, Vol. 6, e22593, 08.06.2017.

Research output: Contribution to journalArticle

Fianco, Giulia ; Mongiardi, Maria Patrizia ; Levi, Andrea ; Luca, Teresa De ; Desideri, Marianna ; Trisciuoglio, Daniela ; Bufalo, Donatella Del ; Cinà, Irene ; Benedetto, Anna Di ; Mottolese, Marcella ; Gentile, Antonietta ; Centonze, Diego ; Ferrè, Fabrizio ; Barilà, Daniela. / Caspase-8 contributes to angiogenesis and chemotherapy resistance in glioblastoma. In: eLife. 2017 ; Vol. 6.
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AU - Trisciuoglio, Daniela

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AU - Cinà, Irene

AU - Benedetto, Anna Di

AU - Mottolese, Marcella

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AU - Barilà, Daniela

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