Cellular prion protein controls stem cell-like properties of human glioblastoma tumor-initiating cells

Alessandro Corsaro, Adriana Bajetto, Stefano Thellung, Giulia Begani, Valentina Villa, Mario Nizzari, Alessandra Pattarozzi, Agnese Solari, Monica Gatti, Aldo Pagano, Roberto Würth, Antonio Daga, Federica Barbieri, Tullio Florio

Research output: Contribution to journalArticle

Abstract

Prion protein (PrPC) is a cell surface glycoprotein whose misfolding is responsible for prion diseases. Although its physiological role is not completely defined, several lines of evidence propose that PrPC is involved in self-renewal, pluripotency gene expression, proliferation and differentiation of neural stem cells. Moreover, PrPC regulates different biological functions in human tumors, including glioblastoma (GBM). We analyzed the role of PrPC in GBM cell pathogenicity focusing on tumorinitiating cells (TICs, or cancer stem cells, CSCs), the subpopulation responsible for development, progression and recurrence of most malignancies. Analyzing four GBM CSC-enriched cultures, we show that PrPC expression is directly correlated with the proliferation rate of the cells. To better define its role in CSC biology, we knocked-down PrPC expression in two of these GBM-derived CSC cultures by specific lentiviral-delivered shRNAs. We provide evidence that CSC proliferation rate, spherogenesis and in vivo tumorigenicity are significantly inhibited in PrPC down-regulated cells. Moreover, PrPC down-regulation caused loss of expression of the stemness and self-renewal markers (NANOG, Sox2) and the activation of differentiation pathways (i.e. increased GFAP expression). Our results suggest that PrPC controls the stemness properties of human GBM CSCs and that its down-regulation induces the acquisition of a more differentiated and less oncogenic phenotype.

Original languageEnglish
Pages (from-to)38638-38657
Number of pages20
JournalOncotarget
Volume7
Issue number25
DOIs
Publication statusPublished - 2016

Keywords

  • Cancer stem cells
  • GFAP
  • Glioblastoma
  • In vivo tumorigenicity
  • Prion protein

ASJC Scopus subject areas

  • Oncology

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    Corsaro, A., Bajetto, A., Thellung, S., Begani, G., Villa, V., Nizzari, M., Pattarozzi, A., Solari, A., Gatti, M., Pagano, A., Würth, R., Daga, A., Barbieri, F., & Florio, T. (2016). Cellular prion protein controls stem cell-like properties of human glioblastoma tumor-initiating cells. Oncotarget, 7(25), 38638-38657. https://doi.org/10.18632/oncotarget.9575