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

Harry Bulstrode; Louise M Jones; Elodie J Siney; Jessica M Sampson; Andreas Ludwig; William P Gray; Sandrine Willaime-Morawek

doi:10.1016/j.canlet.2012.07.022

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

Harry Bulstrode, Louise M Jones, Elodie J Siney, Jessica M Sampson, Andreas Ludwig, William P Gray, Sandrine Willaime-Morawek

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	79-87
Number of pages	9
Journal	Cancer letters
Volume	326
Issue number	1
DOIs	https://doi.org/10.1016/j.canlet.2012.07.022
Publication status	Published - 29 Dec 2012

Keywords

ADAM Proteins
Amyloid Precursor Protein Secretases
Brain Neoplasms
Cell Differentiation
Cell Proliferation
Cell Survival
Glioma
Humans
Membrane Glycoproteins
Membrane Proteins
Neoplastic Stem Cells
Spheroids, Cellular
Tumor Cells, Cultured

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10.1016/j.canlet.2012.07.022

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title = "A-Disintegrin and Metalloprotease (ADAM) 10 and 17 promote self-renewal of brain tumor sphere forming cells",

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.",

keywords = "ADAM Proteins, Amyloid Precursor Protein Secretases, Brain Neoplasms, Cell Differentiation, Cell Proliferation, Cell Survival, Glioma, Humans, Membrane Glycoproteins, Membrane Proteins, Neoplastic Stem Cells, Spheroids, Cellular, Tumor Cells, Cultured",

author = "Harry Bulstrode and Jones, {Louise M} and Siney, {Elodie J} and Sampson, {Jessica M} and Andreas Ludwig and Gray, {William P} and Sandrine Willaime-Morawek",

year = "2012",

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doi = "10.1016/j.canlet.2012.07.022",

language = "English",

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T1 - A-Disintegrin and Metalloprotease (ADAM) 10 and 17 promote self-renewal of brain tumor sphere forming cells

AU - Bulstrode, Harry

AU - Jones, Louise M

AU - Siney, Elodie J

AU - Sampson, Jessica M

AU - Ludwig, Andreas

AU - Gray, William P

AU - Willaime-Morawek, Sandrine

PY - 2012/12/29

Y1 - 2012/12/29

N2 - 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.

AB - 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.

KW - ADAM Proteins

KW - Amyloid Precursor Protein Secretases

KW - Brain Neoplasms

KW - Cell Differentiation

KW - Cell Proliferation

KW - Cell Survival

KW - Glioma

KW - Humans

KW - Membrane Glycoproteins

KW - Membrane Proteins

KW - Neoplastic Stem Cells

KW - Spheroids, Cellular

KW - Tumor Cells, Cultured

U2 - 10.1016/j.canlet.2012.07.022

DO - 10.1016/j.canlet.2012.07.022

M3 - Article

C2 - 22841667

VL - 326

SP - 79

EP - 87

JO - Cancer letters

JF - Cancer letters

SN - 0304-3835

IS - 1

ER -

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

Abstract

Keywords

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