Targeting Ephrin Receptor Tyrosine Kinase A2 with a Selective Aptamer for Glioblastoma Stem Cells

Alessandra Affinito, Cristina Quintavalle, Carla Lucia Esposito, Giuseppina Roscigno, Catello Giordano, Silvia Nuzzo, Lucia Ricci-Vitiani, Iolanda Scognamiglio, Zoran Minic, Roberto Pallini, Maxim V. Berezovski, Vittorio de Francisis, Gerolama Condorelli

Research output: Contribution to journalArticlepeer-review

Abstract

Despite the benefits associated with radiotherapy and chemotherapy for glioblastoma (GBM) treatment, most patients experience a relapse following initial therapy. Recurrent or progressive GBM usually does not respond anymore to standard therapy, and this is associated with poor patient outcome. GBM stem cells (GSCs) are a subset of cells resistant to radiotherapy and chemotherapy and play a role in tumor recurrence. The targeting of GSCs and the identification of novel markers are crucial issues in the development of innovative strategies for GBM eradication. By differential cell SELEX (systematic evolution of ligands by exponential enrichment), we have recently described two RNA aptamers, that is, the 40L sequence and its truncated form A40s, able to bind the cell surface of human GSCs. Both aptamers were selective for stem-like growing GBM cells and are rapidly internalized into target cells. In this study, we demonstrate that their binding to cells is mediated by direct recognition of the ephrin type-A receptor 2 (EphA2). Functionally, the two aptamers were able to inhibit cell growth, stemness, and migration of GSCs. Furthermore, A40s was able to cross the blood-brain barrier (BBB) and was stable in serum in in vitro experiments. These results suggest that 40L and A40s represent innovative potential therapeutic tools for GBM.

Original languageEnglish
Pages (from-to)176-185
Number of pages10
JournalMolecular Therapy - Nucleic Acids
Volume20
DOIs
Publication statusPublished - Jun 5 2020

Keywords

  • aptamer
  • cancer stem cell
  • cancer therapy
  • EphA2
  • glioblastoma
  • GSCs
  • RNA
  • therapeutic RNAs

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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