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Integrin α10, a novel therapeutic target in glioblastoma, regulates cell migration, proliferation, and survival

Thorén, Matilda Munksgaard LU ; Masoumi, Katarzyna Chmielarska LU ; Krona, Cecilia ; Huang, Xiaoli ; Kundu, Soumi ; Schmidt, Linnéa ; Forsberg-Nilsson, Karin ; Keep, Marcus Floyd ; Englund, Elisabet LU orcid and Nelander, Sven , et al. (2019) In Cancers 11(4).
Abstract

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 a10 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... (More)

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 a10 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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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Antibody-drug conjugate (ADC), Glioblastoma (GBM), Glioma, Integrin α10, Saporin
in
Cancers
volume
11
issue
4
article number
587
publisher
MDPI AG
external identifiers
  • scopus:85071883972
  • pmid:31027305
ISSN
2072-6694
DOI
10.3390/cancers11040587
language
English
LU publication?
yes
id
50e4d24e-7e81-4f24-b79f-d0db367a2bdb
date added to LUP
2019-09-23 11:02:24
date last changed
2024-07-10 03:04:15
@article{50e4d24e-7e81-4f24-b79f-d0db367a2bdb,
  abstract     = {{<p>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 a10 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.</p>}},
  author       = {{Thorén, Matilda Munksgaard and Masoumi, Katarzyna Chmielarska and Krona, Cecilia and Huang, Xiaoli and Kundu, Soumi and Schmidt, Linnéa and Forsberg-Nilsson, Karin and Keep, Marcus Floyd and Englund, Elisabet and Nelander, Sven and Holmqvist, Bo and Lundgren-Åkerlund, Evy}},
  issn         = {{2072-6694}},
  keywords     = {{Antibody-drug conjugate (ADC); Glioblastoma (GBM); Glioma; Integrin α10; Saporin}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{4}},
  publisher    = {{MDPI AG}},
  series       = {{Cancers}},
  title        = {{Integrin α10, a novel therapeutic target in glioblastoma, regulates cell migration, proliferation, and survival}},
  url          = {{http://dx.doi.org/10.3390/cancers11040587}},
  doi          = {{10.3390/cancers11040587}},
  volume       = {{11}},
  year         = {{2019}},
}