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Cited by 35Glioma Diagnosis and TreatmentProtease and Inhibitor MechanismsCancer Cells and Metastasis

Metalloproteinases ADAM10 and ADAM17 Mediate Migration and Differentiation in Glioblastoma Sphere-Forming Cells

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Siney, Elodie J., Holden, Alexander, Casselden, Elizabeth, Bulstrode, Harry, Thomas, Gareth J., Willaime-Morawek, Sandrine·2017·Molecular Neurobiology
DOI 10.1007/s12035-016-0053-6PMC PMC5443867
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Abstract

Glioblastoma is the most common form of primary malignant brain tumour. These tumours are highly proliferative and infiltrative resulting in a median patient survival of only 14 months from diagnosis. The current treatment regimens are ineffective against the small population of cancer stem cells residing in the tumourigenic niche; however, a new therapeutic approach could involve the removal of these cells from the microenvironment that maintains the cancer stem cell phenotype. We have isolated multipotent sphere-forming cells from human high grade glioma (glioma sphere-forming cells (GSCs)) to investigate the adhesive and migratory properties of these cells in vitro. We have focused on the role of two closely related metalloproteinases ADAM10 and ADAM17 due to their high expression in glioblastoma and GSCs and their ability to activate cytokines and growth factors. Here, we report that ADAM10 and ADAM17 inhibition selectively increases GSC, but not neural stem cell, migration and that the migrated GSCs exhibit a differentiated phenotype. We also observed a correlation between nestin, a stem/progenitor marker, and fibronectin, an extracellular matrix protein, expression in high grade glioma tissues. GSCs adherence on fibronectin is mediated by α5β1 integrin, where fibronectin further promotes GSC migration and is an effective candidate for in vivo cancer stem cell migration out of the tumourigenic niche. Our results suggest that therapies against ADAM10 and ADAM17 may promote cancer stem cell migration away from the tumourigenic niche resulting in a differentiated phenotype that is more susceptible to treatment.

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  • The α-secretase ADAM10 is functionally associated with several integrins.

    “Finally, the α-secretase ADAM10 has been functionally associated with several integrins [62, 121].”

    From The new genetic landscape of Alzheimer’s disease: from amyloid cascade to genetically driven synaptic failure hypothesis? (2019) · cites this paper as [121]

    The Results section, “GSC Adhesion to Fibronectin Is Mediated by Integrin α5β1” (page unavailable), reports findings suggesting that ADAM10 interacts with β1 integrin in glioblastoma sphere-forming cells. The Discussion also discusses a possible ADAM–integrin interaction. These passages support a functional association, but they do not establish ADAM10 associations with several distinct integrins. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Siney, E. J., Holden, A., Casselden, E., Bulstrode, H., Thomas, G. J., & Willaime-Morawek, S.
Affiliations
  • Southampton General Hospital (GB)
  • University of Southampton (GB)
  • University Hospital Southampton NHS Foundation Trust (GB)
Corresponding author
Siney, Elodie J.
ORCID
Venue
Molecular Neurobiology
Publisher
Springer Science and Business Media LLC
Published
2016-08-19
Volume
54
Issue
5
Pages
3893-3905
ISSN
  • 0893-7648 (ISSN-L)
  • 1559-1182
DOI
10.1007/s12035-016-0053-6
PMC
PMC5443867
OpenAlex
W2513561817
Cited by
35
References
1
Citations by year
2026: 1 · 2025: 2 · 2024: 4 · 2023: 5 · 2022: 2 · 2021: 4 · 2019: 6 · 2018: 4 · 2017: 7
FWCI
3.47
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Neurobiology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ePrints Soton (University of Southampton) (acceptedVersion)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo (cc-by)
Funders
  • Medical Research Council
  • Wessex Medical Trust
  • The Royal Society
  • Wessex Brian Tumour fund
Topics
  • Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
glioblastoma, ADAM10, ADAM17, metalloproteinases, cancer stem cells, cell migration, cell differentiation, fibronectin, alpha5beta1 integrin, nestin, extracellular matrix, tumor microenvironment
MeSH terms
ADAM10 Protein, ADAM17 Protein, Adult, Aged, Cell Differentiation, Cell Movement, Extracellular Matrix, Female, Fibronectins, Glioblastoma, Humans, Male, Middle Aged, Neoplastic Stem Cells, Cell Death, Spheroids, Cellular, Integrin alpha5beta1, Neural Stem Cells, Matrix Metalloproteinase Inhibitors

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