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, 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., Integrin α7 Is a Functional Marker and Potential Therapeutic Target in Glioblastoma, <<CELL STEM CELL>>, 2017; 21 (1): 35-50.e9. [doi:10.1016/j.stem.2017.04.009] [http://hdl.handle.net/10807/106304]

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

Haas, Tobias Longin
Primo
;
Sciuto, Maria Rita
Secondo
;
Valvo, Cecilia;Fiori, Micol Eleonora;Giannetti, Stefano;Morgante, Liliana;Pallini, Roberto
Penultimo
;
De Maria, R.
2017

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.
Inglese
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., Integrin α7 Is a Functional Marker and Potential Therapeutic Target in Glioblastoma, <<CELL STEM CELL>>, 2017; 21 (1): 35-50.e9. [doi:10.1016/j.stem.2017.04.009] [http://hdl.handle.net/10807/106304]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/106304
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