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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)35-50.e9
JournalCell Stem Cell
Volume21
Issue number1
DOIs
Publication statusPublished - Jul 6 2017

    Fingerprint

Keywords

  • biomarker
  • cancer stem cell marker
  • glioblastoma cell invasion
  • high throughput screening
  • mAb
  • monoclonal antibody

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

Cite this

Haas, T. L., Sciuto, M. R., Brunetto, L., Valvo, C., Signore, M., Fiori, M. E., di Martino, S., Giannetti, S., Morgante, L., Boe, A., Patrizii, M., Warnken, U., Schnölzer, M., Ciolfi, A., Di Stefano, C., Biffoni, M., Ricci-Vitiani, L., Pallini, R., & De Maria, R. (2017). Integrin α7 Is a Functional Marker and Potential Therapeutic Target in Glioblastoma. Cell Stem Cell, 21(1), 35-50.e9. https://doi.org/10.1016/j.stem.2017.04.009