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Novel association between microglia and stem cells in human gliomas: a contributor to tumour proliferation?

Novel association between microglia and stem cells in human gliomas: a contributor to tumour proliferation?
Novel association between microglia and stem cells in human gliomas: a contributor to tumour proliferation?
Brain tumour stem cells and microglia both promote the growth of astrocytomas, the commonest form of primary brain tumour, with recent emerging evidence that these cell types may interact in glioma models. It is unclear whether microglia and stem cells are associated in human gliomas. To investigate this question, we used the technique of tissue microarrays to perform a correlative study of a large number of tumour samples. We quantified immunostaining of human astrocytic tumour tissue microarrays (86 patients; World Health Organisation grade II–IV) for microglia Ionized calcium binding adaptor molecule 1 (Iba1) and CD68, and stem cell nestin, SOX2 and CD133. Ki67 was used to assess proliferation and GFAP for astrocytic differentiation. Immunoreactivity for both microglial markers and stem cell markers nestin and SOX2 significantly increased with increasing tumour grade. GFAP was higher in low grade astrocytomas. There was a positive correlation between: (i) both microglial markers and nestin and CD133, (ii) nestin and tumour cell proliferation Ki67 and (iii) both microglial markers and Ki67. SOX2 was not associated with microglia or tumour proliferation. To test the clinical relevance, we investigated the putative association of these markers with clinical outcomes. High expression for nestin and Iba1 correlated with significantly shorter survival times, and high expression for nestin, Iba1, CD68 and Ki67 was associated with faster tumour progression on univariate analysis. On multivariate analysis, nestin, CD133 and Ki67 remained significant predictors of poorer survival, after adjustment for other markers. These results confirm previous in vitro findings, demonstrating their functional relevance as a therapeutic target in humans. This is the first report of a novel correlation between microglia and stem cells that may drive human astrocytic tumour development.
glioma, microglia, stem cells, brain tumour
67-75
Noorani, Imran
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Petty, Gareth
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Grundy, Paul L
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Sharpe, Geoff
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Willaime-Morawek, Sandrine
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Harris, Scott
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Thomas, Gareth J
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Nicoll, James AR
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Noorani, Imran
d73f97c0-2dc7-4d7e-be31-e2d2f0b3131d
Petty, Gareth
289f8af0-9776-4bb3-936f-5d92343965bb
Grundy, Paul L
7271ed29-034d-42af-bbf0-628d53c71646
Sharpe, Geoff
0fd4e12a-196d-45ba-9f1d-3c668bfced52
Willaime-Morawek, Sandrine
24a2981f-aa9e-4bf6-ad12-2ccf6b49f1c0
Harris, Scott
19ea097b-df15-4f0f-be19-8ac42c190028
Thomas, Gareth J
2ff54aa9-a766-416b-91ee-cf1c5be74106
Nicoll, James AR
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61

Noorani, Imran, Petty, Gareth, Grundy, Paul L, Sharpe, Geoff, Willaime-Morawek, Sandrine, Harris, Scott, Thomas, Gareth J, Nicoll, James AR and Boche, Delphine (2015) Novel association between microglia and stem cells in human gliomas: a contributor to tumour proliferation? The Journal of Pathology: Clinical Research, 1 (2), 67-75. (doi:10.1002/CJP2.7).

Record type: Article

Abstract

Brain tumour stem cells and microglia both promote the growth of astrocytomas, the commonest form of primary brain tumour, with recent emerging evidence that these cell types may interact in glioma models. It is unclear whether microglia and stem cells are associated in human gliomas. To investigate this question, we used the technique of tissue microarrays to perform a correlative study of a large number of tumour samples. We quantified immunostaining of human astrocytic tumour tissue microarrays (86 patients; World Health Organisation grade II–IV) for microglia Ionized calcium binding adaptor molecule 1 (Iba1) and CD68, and stem cell nestin, SOX2 and CD133. Ki67 was used to assess proliferation and GFAP for astrocytic differentiation. Immunoreactivity for both microglial markers and stem cell markers nestin and SOX2 significantly increased with increasing tumour grade. GFAP was higher in low grade astrocytomas. There was a positive correlation between: (i) both microglial markers and nestin and CD133, (ii) nestin and tumour cell proliferation Ki67 and (iii) both microglial markers and Ki67. SOX2 was not associated with microglia or tumour proliferation. To test the clinical relevance, we investigated the putative association of these markers with clinical outcomes. High expression for nestin and Iba1 correlated with significantly shorter survival times, and high expression for nestin, Iba1, CD68 and Ki67 was associated with faster tumour progression on univariate analysis. On multivariate analysis, nestin, CD133 and Ki67 remained significant predictors of poorer survival, after adjustment for other markers. These results confirm previous in vitro findings, demonstrating their functional relevance as a therapeutic target in humans. This is the first report of a novel correlation between microglia and stem cells that may drive human astrocytic tumour development.

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Accepted/In Press date: 25 September 2014
e-pub ahead of print date: 14 January 2015
Published date: April 2015
Keywords: glioma, microglia, stem cells, brain tumour
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 373424
URI: http://eprints.soton.ac.uk/id/eprint/373424
PURE UUID: 88158616-2591-4b24-a831-45c770383121
ORCID for Sandrine Willaime-Morawek: ORCID iD orcid.org/0000-0002-1121-6419
ORCID for James AR Nicoll: ORCID iD orcid.org/0000-0002-9444-7246
ORCID for Delphine Boche: ORCID iD orcid.org/0000-0002-5884-130X

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Date deposited: 16 Jan 2015 16:45
Last modified: 18 Feb 2021 17:11

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Contributors

Author: Imran Noorani
Author: Gareth Petty
Author: Paul L Grundy
Author: Geoff Sharpe
Author: Scott Harris
Author: Gareth J Thomas
Author: James AR Nicoll ORCID iD
Author: Delphine Boche ORCID iD

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