Functionally relevant markers of glioblastoma stem- like cells (GSCs) have potential for therapeutic tar- geting 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 compre- hensive datasets revealed that high ITGA7 expres- sion 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 thera- peutic 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 Marchiano, R., Integrin a7 Is a Functional Marker and Potential Therapeutic Target in Glioblastoma, <<CELL STEM CELL>>, 2017; (21 (1)): 35-50. [doi:10.1016/j.stem.2017.04.009] [http://hdl.handle.net/10807/111256]
Integrin a7 Is a Functional Marker and Potential Therapeutic Target in Glioblastoma
Haas, Tobias Longin;Sciuto, Maria Rita;Valvo, Cecilia;Fiori, Micol Eleonora;Di Martino, Susanna;Giannetti, Stefano;Morgante, Liliana;Pallini, Roberto;De Maria Marchiano, Ruggero
2017
Abstract
Functionally relevant markers of glioblastoma stem- like cells (GSCs) have potential for therapeutic tar- geting 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 compre- hensive datasets revealed that high ITGA7 expres- sion 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 thera- peutic target.
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