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

Research output: Contribution to journalArticle

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 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.

Details

Authors
  • 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
Organisations
External organisations
  • Xintela AB
  • Uppsala University
  • University of North Dakota
  • ImaGene-iT AB
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • Antibody-drug conjugate (ADC), Glioblastoma (GBM), Glioma, Integrin α10, Saporin
Original languageEnglish
Article number587
JournalCancers
Volume11
Issue number4
Publication statusPublished - 2019 Apr 25
Publication categoryResearch
Peer-reviewedYes