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Integrin a7 Is a Functional Marker and Potential Therapeutic Target in Glioblastoma

Authors :
Haas, Tobias Longin
Sciuto, Maria Rita
Brunetto, L
Valvo, Cecilia
Signore, M
Fiori, Micol Eleonora
Di Martino, Susanna
Giannetti, Stefano
Morgante, Liliana
Boe, A
Patrizii, M
Warnken, U
Schnölzer, M
Ciolfi, A
Di Stefano, C
Biffoni, M
Ricci-Vitiani, L
Pallini, Roberto
De Maria Marchiano, Ruggero
Haas TL (ORCID:0000-0003-2336-0263)
Sciuto MR
Valvo C
Fiori ME
di Martino S
Giannetti S (ORCID:0000-0002-9456-8865)
Morgante L
Pallini R (ORCID:0000-0002-4611-8827)
De Maria Marchiano R. (ORCID:0000-0003-2255-0583)
Haas, Tobias Longin
Sciuto, Maria Rita
Brunetto, L
Valvo, Cecilia
Signore, M
Fiori, Micol Eleonora
Di Martino, Susanna
Giannetti, Stefano
Morgante, Liliana
Boe, A
Patrizii, M
Warnken, U
Schnölzer, M
Ciolfi, A
Di Stefano, C
Biffoni, M
Ricci-Vitiani, L
Pallini, Roberto
De Maria Marchiano, Ruggero
Haas TL (ORCID:0000-0003-2336-0263)
Sciuto MR
Valvo C
Fiori ME
di Martino S
Giannetti S (ORCID:0000-0002-9456-8865)
Morgante L
Pallini R (ORCID:0000-0002-4611-8827)
De Maria Marchiano R. (ORCID:0000-0003-2255-0583)
Publication Year :
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.

Details

Database :
OAIster
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1105031298
Document Type :
Electronic Resource