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A-Disintegrin and metalloprotease (ADAM) 10 and 17 promote self-renewal of brain tumor sphere forming cells

A-Disintegrin and metalloprotease (ADAM) 10 and 17 promote self-renewal of brain tumor sphere forming cells
A-Disintegrin and metalloprotease (ADAM) 10 and 17 promote self-renewal of brain tumor sphere forming cells
It has been proposed that gliomas contain a subpopulation of 'Brain Tumor Stem Cells' (BTSCs), which demonstrate resistance to conventional therapies. A potential component of the environment governing the behavior of these BTSCs is a class of transmembrane proteins with structural and signaling functions, the A-Disintegrin And Metalloproteases (ADAMs). In this study we confirm overexpression of ADAM10 and 17 in human glioma tissue compared to human controls, and especially in tumor sphere cultures thought to enrich for BTSCs. Inhibition of ADAM10/17 function impairs the growth of tumor spheres with evidence of depletion of the sphere forming cell population. This results from a combination of reduced proliferation, cell death and a switch of sphere-forming cells away from symmetric self-renewal division towards neuronal differentiation. A developing appreciation of the role of ADAMs in BTSC promises insights into pathophysiology and potential therapeutic avenues in this intractable group of tumors.
brain tumor, ADAM10, ADAM17
0304-3835
79-87
Bulstrode, Harry
7d977124-acda-4e5f-91b5-183105c297f7
Jones, Louise M
30a3af86-89ca-4091-bd8b-b9448a293d0a
Siney, Elodie J
2936defd-b396-4c59-86d5-ea258e427094
Sampson, Jessica M
5ec4d8c2-abbd-4ebe-94ab-677b68f4d5f1
Ludwig, Andreas
58edc4b0-f8b6-4422-a652-dc771a06fe70
Gray, William P
dde0eca1-7d39-451d-8914-2cb95f65e025
Willaime-Morawek, Sandrine
24a2981f-aa9e-4bf6-ad12-2ccf6b49f1c0
Bulstrode, Harry
7d977124-acda-4e5f-91b5-183105c297f7
Jones, Louise M
30a3af86-89ca-4091-bd8b-b9448a293d0a
Siney, Elodie J
2936defd-b396-4c59-86d5-ea258e427094
Sampson, Jessica M
5ec4d8c2-abbd-4ebe-94ab-677b68f4d5f1
Ludwig, Andreas
58edc4b0-f8b6-4422-a652-dc771a06fe70
Gray, William P
dde0eca1-7d39-451d-8914-2cb95f65e025
Willaime-Morawek, Sandrine
24a2981f-aa9e-4bf6-ad12-2ccf6b49f1c0

Bulstrode, Harry, Jones, Louise M, Siney, Elodie J, Sampson, Jessica M, Ludwig, Andreas, Gray, William P and Willaime-Morawek, Sandrine (2012) A-Disintegrin and metalloprotease (ADAM) 10 and 17 promote self-renewal of brain tumor sphere forming cells. Cancer Letters, 326 (1), 79-87. (doi:10.1016/j.canlet.2012.07.022). (PMID:22841667)

Record type: Article

Abstract

It has been proposed that gliomas contain a subpopulation of 'Brain Tumor Stem Cells' (BTSCs), which demonstrate resistance to conventional therapies. A potential component of the environment governing the behavior of these BTSCs is a class of transmembrane proteins with structural and signaling functions, the A-Disintegrin And Metalloproteases (ADAMs). In this study we confirm overexpression of ADAM10 and 17 in human glioma tissue compared to human controls, and especially in tumor sphere cultures thought to enrich for BTSCs. Inhibition of ADAM10/17 function impairs the growth of tumor spheres with evidence of depletion of the sphere forming cell population. This results from a combination of reduced proliferation, cell death and a switch of sphere-forming cells away from symmetric self-renewal division towards neuronal differentiation. A developing appreciation of the role of ADAMs in BTSC promises insights into pathophysiology and potential therapeutic avenues in this intractable group of tumors.

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Accepted/In Press date: 24 July 2012
Published date: 29 December 2012
Keywords: brain tumor, ADAM10, ADAM17
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 341679
URI: https://eprints.soton.ac.uk/id/eprint/341679
ISSN: 0304-3835
PURE UUID: 0e85c358-50c8-4590-8501-f1decffe2a28
ORCID for Sandrine Willaime-Morawek: ORCID iD orcid.org/0000-0002-1121-6419

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Date deposited: 02 Aug 2012 12:20
Last modified: 29 Oct 2019 01:46

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Contributors

Author: Harry Bulstrode
Author: Louise M Jones
Author: Elodie J Siney
Author: Jessica M Sampson
Author: Andreas Ludwig
Author: William P Gray

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