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Integrin alpha 10, a Novel Therapeutic Target in Glioblastoma, Regulates Cell Migration, Proliferation, and Survival
Xintela AB, SE-22381 Lund, Sweden.
Xintela AB, SE-22381 Lund, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Xintela AB, SE-22381 Lund, Sweden.
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2019 (English)In: Cancers, ISSN 2072-6694, Vol. 11, no 4, article id 587Article in journal (Refereed) Published
Abstract [en]

New, effective treatment strategies for glioblastomas (GBMs), the most malignant and invasive brain tumors in adults, are highly needed. In this study, we investigated the potential of integrin alpha 10 beta 1 as a therapeutic target in GBMs. Expression levels and the role of integrin alpha 10 beta 1 were studied in patient-derived GBM tissues and cell lines. The effect of an antibody-drug conjugate (ADC), an integrin alpha 10 antibody conjugated to saporin, on GBM cells and in a xenograft mouse model was studied. We found that integrin alpha 10 beta 1 was strongly expressed in both GBM tissues and cells, whereas morphologically unaffected brain tissues showed only minor expression. Partial or no overlap was seen with integrins alpha 3, alpha 6, and alpha 7, known to be expressed in GBM. Further analysis of a subpopulation of GBM cells selected for high integrin alpha 10 expression demonstrated increased proliferation and sphere formation. Additionally, siRNA-mediated knockdown of integrin alpha 10 in GBM cells led to decreased migration and increased cell death. Furthermore, the ADC reduced viability and sphere formation of GBM cells and induced cell death both in vitro and in vivo. Our results demonstrate that integrin alpha 10 beta 1 has a functional role in GBM cells and is a novel, potential therapeutic target for the treatment of GBM.

Place, publisher, year, edition, pages
MDPI , 2019. Vol. 11, no 4, article id 587
Keywords [en]
glioblastoma (GBM), glioma, integrin alpha 10, antibody-drug conjugate (ADC), saporin
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:uu:diva-385567DOI: 10.3390/cancers11040587ISI: 000467773400155PubMedID: 31027305OAI: oai:DiVA.org:uu-385567DiVA, id: diva2:1327072
Available from: 2019-06-19 Created: 2019-06-19 Last updated: 2019-06-19Bibliographically approved

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