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Open AccessArticle

Integrin α10, a Novel Therapeutic Target in Glioblastoma, Regulates Cell Migration, Proliferation, and Survival

1
Xintela AB, Medicon Village, SE-223 81 Lund, Sweden
2
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden
3
Department of Neurosurgery, Sanford Brain and Spine Institute, Fargo, ND 58103, USA; Department of Surgery, School of Medicine, University of North Dakota, Fargo, ND 58102, USA
4
Neuropathology Lab, Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, SE-221 84 Lund, Sweden
5
ImaGene-iT AB, Medicon Village, SE-223 81 Lund, Sweden
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(4), 587; https://doi.org/10.3390/cancers11040587
Received: 22 March 2019 / Revised: 18 April 2019 / Accepted: 23 April 2019 / Published: 25 April 2019
(This article belongs to the Special Issue The Role of Integrins in Cancer)
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 α10β1 as a therapeutic target in GBMs. Expression levels and the role of integrin α10β1 were studied in patient-derived GBM tissues and cell lines. The effect of an antibody–drug conjugate (ADC), an integrin α10 antibody conjugated to saporin, on GBM cells and in a xenograft mouse model was studied. We found that integrin α10β1 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 α3, α6, and α7, known to be expressed in GBM. Further analysis of a subpopulation of GBM cells selected for high integrin α10 expression demonstrated increased proliferation and sphere formation. Additionally, siRNA-mediated knockdown of integrin α10 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 α10β1 has a functional role in GBM cells and is a novel, potential therapeutic target for the treatment of GBM. View Full-Text
Keywords: glioblastoma (GBM); glioma; integrin α10; antibody–drug conjugate (ADC); saporin glioblastoma (GBM); glioma; integrin α10; antibody–drug conjugate (ADC); saporin
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Munksgaard Thorén, M.; Chmielarska Masoumi, K.; Krona, C.; Huang, X.; Kundu, S.; Schmidt, L.; Forsberg-Nilsson, K.; Floyd Keep, M.; Englund, E.; Nelander, S.; Holmqvist, B.; Lundgren-Åkerlund, E. Integrin α10, a Novel Therapeutic Target in Glioblastoma, Regulates Cell Migration, Proliferation, and Survival. Cancers 2019, 11, 587.

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