Functionally relevant markers of glioblastoma stemlike 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 a7 (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.
Integrin α7 is a functional marker and potential therapeutic target in glioblastoma / Haas, Tobias L.; Rita Sciuto, Maria; Brunetto, Lidia; Valvo, Cecilia; Signore, Michele; Fiori, Micol E.; DI MARTINO, Simona; Giannetti, Stefano; Morgante, Liliana; Boe, Alessandra; Patrizii, Michele; Warnken, Uwe; Schnolzer, Martina; Ciolfi, Andrea; DI STEFANO, Chiara; Biffoni, Mauro; Ricci-Vitiani, Lucia; Pallini, Roberto; Ruggero De Maria, And. - In: CELL STEM CELL. - ISSN 1934-5909. - 21:1(2017), pp. 35-50.e9. [10.1016/j.stem.2017.04.009]
Integrin α7 is a functional marker and potential therapeutic target in glioblastoma
BRUNETTO, LIDIA;Michele Signore;Micol E. Fiori;Simona di Martino;Andrea Ciolfi;Chiara Di Stefano;
2017
Abstract
Functionally relevant markers of glioblastoma stemlike 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 a7 (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.File | Dimensione | Formato | |
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