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

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 pa...

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Autores principales: Munksgaard Thorén, Matilda, Chmielarska Masoumi, Katarzyna, Krona, Cecilia, Huang, Xiaoli, Kundu, Soumi, Schmidt, Linnéa, Forsberg-Nilsson, Karin, Floyd Keep, Marcus, Englund, Elisabet, Nelander, Sven, Holmqvist, Bo, Lundgren-Åkerlund, Evy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521287/
https://www.ncbi.nlm.nih.gov/pubmed/31027305
http://dx.doi.org/10.3390/cancers11040587
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author Munksgaard Thorén, Matilda
Chmielarska Masoumi, Katarzyna
Krona, Cecilia
Huang, Xiaoli
Kundu, Soumi
Schmidt, Linnéa
Forsberg-Nilsson, Karin
Floyd Keep, Marcus
Englund, Elisabet
Nelander, Sven
Holmqvist, Bo
Lundgren-Åkerlund, Evy
author_facet Munksgaard Thorén, Matilda
Chmielarska Masoumi, Katarzyna
Krona, Cecilia
Huang, Xiaoli
Kundu, Soumi
Schmidt, Linnéa
Forsberg-Nilsson, Karin
Floyd Keep, Marcus
Englund, Elisabet
Nelander, Sven
Holmqvist, Bo
Lundgren-Åkerlund, Evy
author_sort Munksgaard Thorén, Matilda
collection PubMed
description 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.
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spelling pubmed-65212872019-05-31 Integrin α10, a Novel Therapeutic Target in Glioblastoma, Regulates Cell Migration, Proliferation, and Survival Munksgaard Thorén, Matilda Chmielarska Masoumi, Katarzyna Krona, Cecilia Huang, Xiaoli Kundu, Soumi Schmidt, Linnéa Forsberg-Nilsson, Karin Floyd Keep, Marcus Englund, Elisabet Nelander, Sven Holmqvist, Bo Lundgren-Åkerlund, Evy Cancers (Basel) Article 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. MDPI 2019-04-25 /pmc/articles/PMC6521287/ /pubmed/31027305 http://dx.doi.org/10.3390/cancers11040587 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Munksgaard Thorén, Matilda
Chmielarska Masoumi, Katarzyna
Krona, Cecilia
Huang, Xiaoli
Kundu, Soumi
Schmidt, Linnéa
Forsberg-Nilsson, Karin
Floyd Keep, Marcus
Englund, Elisabet
Nelander, Sven
Holmqvist, Bo
Lundgren-Åkerlund, Evy
Integrin α10, a Novel Therapeutic Target in Glioblastoma, Regulates Cell Migration, Proliferation, and Survival
title Integrin α10, a Novel Therapeutic Target in Glioblastoma, Regulates Cell Migration, Proliferation, and Survival
title_full Integrin α10, a Novel Therapeutic Target in Glioblastoma, Regulates Cell Migration, Proliferation, and Survival
title_fullStr Integrin α10, a Novel Therapeutic Target in Glioblastoma, Regulates Cell Migration, Proliferation, and Survival
title_full_unstemmed Integrin α10, a Novel Therapeutic Target in Glioblastoma, Regulates Cell Migration, Proliferation, and Survival
title_short Integrin α10, a Novel Therapeutic Target in Glioblastoma, Regulates Cell Migration, Proliferation, and Survival
title_sort integrin α10, a novel therapeutic target in glioblastoma, regulates cell migration, proliferation, and survival
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521287/
https://www.ncbi.nlm.nih.gov/pubmed/31027305
http://dx.doi.org/10.3390/cancers11040587
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