Integrin α7 Is a Functional Marker and Potential Therapeutic Target in Glioblastoma

Tobias Longin Haas, Stefano Giannetti, Roberto Pallini, Ruggero De Maria Marchiano, Maria Rita Sciuto, Cecilia Valvo, Micol Eleonora Fiori, Liliana Morgante, Lidia Brunetto, Michele Signore, Simona Di Martino, Alessandra Boe, Michele Patrizii, Uwe Warnken, Martina Schnölzer, Andrea Ciolfi, Chiara Di Stefano, Mauro Biffoni, Lucia Ricci-Vitiani

Risultato della ricerca: Contributo in rivistaArticolo in rivista

53 Citazioni (Scopus)

Abstract

Functionally relevant markers of glioblastoma stem-like cells (GSCs) have potential for therapeutic targeting to treat this aggressive disease. Here we used generation and screening of thousands of monoclonal antibodies to search for receptors and signaling pathways preferentially enriched in GSCs. We identified integrin α7 (ITGA7) as a major laminin receptor in GSCs and in primary high-grade glioma specimens. Analyses of mRNA profiles in comprehensive datasets revealed that high ITGA7 expression negatively correlated with survival of patients with both low- and high-grade glioma. In vitro and in vivo analyses showed that ITGA7 plays a key functional role in growth and invasiveness of GSCs. We also found that targeting of ITGA7 by RNAi or blocking mAbs impaired laminin-induced signaling, and it led to a significant delay in tumor engraftment plus a strong reduction in tumor size and invasion. Our data, therefore, highlight ITGA7 as a glioblastoma biomarker and candidate therapeutic target. Haas et al. identify integrin α7 as a functional marker of glioblastoma stem cells by screening a monoclonal antibody library generated against primary glioblastoma (GBM) cells. Functional experiments in culture and in vivo show that the targeting of integrin α7 has potential as a therapeutic avenue for treating this aggressive disease.
Lingua originaleEnglish
pagine (da-a)35-50.e9
RivistaCell Stem Cell
Volume21
DOI
Stato di pubblicazionePubblicato - 2017

Keywords

  • Cell Biology
  • Genetics
  • Molecular Medicine
  • biomarker
  • cancer stem cell marker
  • glioblastoma cell invasion
  • high throughput screening
  • mAb
  • monoclonal antibody

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