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 &#...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/4/587 |
| _version_ | 1797712132547018752 |
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| author | Matilda Munksgaard Thorén Katarzyna Chmielarska Masoumi Cecilia Krona Xiaoli Huang Soumi Kundu Linnéa Schmidt Karin Forsberg-Nilsson Marcus Floyd Keep Elisabet Englund Sven Nelander Bo Holmqvist Evy Lundgren-Åkerlund |
| author_facet | Matilda Munksgaard Thorén Katarzyna Chmielarska Masoumi Cecilia Krona Xiaoli Huang Soumi Kundu Linnéa Schmidt Karin Forsberg-Nilsson Marcus Floyd Keep Elisabet Englund Sven Nelander Bo Holmqvist Evy Lundgren-Åkerlund |
| author_sort | Matilda Munksgaard Thorén |
| collection | DOAJ |
| 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 <em>in vitro </em>and <em>in vivo</em>. 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. |
| first_indexed | 2024-03-12T07:17:16Z |
| format | Article |
| id | doaj.art-7b822b5b52d24ad0ab8885ed08f11bc1 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T07:17:16Z |
| publishDate | 2019-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-7b822b5b52d24ad0ab8885ed08f11bc12023-09-02T22:41:46ZengMDPI AGCancers2072-66942019-04-0111458710.3390/cancers11040587cancers11040587Integrin α10, a Novel Therapeutic Target in Glioblastoma, Regulates Cell Migration, Proliferation, and SurvivalMatilda Munksgaard Thorén0Katarzyna Chmielarska Masoumi1Cecilia Krona2Xiaoli Huang3Soumi Kundu4Linnéa Schmidt5Karin Forsberg-Nilsson6Marcus Floyd Keep7Elisabet Englund8Sven Nelander9Bo Holmqvist10Evy Lundgren-Åkerlund11Xintela AB, Medicon Village, SE-223 81 Lund, SwedenXintela AB, Medicon Village, SE-223 81 Lund, SwedenDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, SwedenXintela AB, Medicon Village, SE-223 81 Lund, SwedenDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, SwedenXintela AB, Medicon Village, SE-223 81 Lund, SwedenDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, SwedenDepartment of Neurosurgery, Sanford Brain and Spine Institute, Fargo, ND 58103, USA; Department of Surgery, School of Medicine, University of North Dakota, Fargo, ND 58102, USANeuropathology Lab, Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, SE-221 84 Lund, SwedenDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, SwedenImaGene-iT AB, Medicon Village, SE-223 81 Lund, SwedenXintela AB, Medicon Village, SE-223 81 Lund, SwedenNew, 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 <em>in vitro </em>and <em>in vivo</em>. 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.https://www.mdpi.com/2072-6694/11/4/587glioblastoma (GBM)gliomaintegrin α10antibody–drug conjugate (ADC)saporin |
| spellingShingle | Matilda Munksgaard Thorén Katarzyna Chmielarska Masoumi Cecilia Krona Xiaoli Huang Soumi Kundu Linnéa Schmidt Karin Forsberg-Nilsson Marcus Floyd Keep Elisabet Englund Sven Nelander Bo Holmqvist Evy Lundgren-Åkerlund Integrin α10, a Novel Therapeutic Target in Glioblastoma, Regulates Cell Migration, Proliferation, and Survival Cancers glioblastoma (GBM) glioma integrin α10 antibody–drug conjugate (ADC) saporin |
| 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 | glioblastoma (GBM) glioma integrin α10 antibody–drug conjugate (ADC) saporin |
| url | https://www.mdpi.com/2072-6694/11/4/587 |
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