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The role of astrocytes in CNS tumors: pre-clinical models and novel imaging approaches

Brain metastasis is a significant clinical problem, yet the mechanisms governing tumor cell extravasation across the blood-brain barrier (BBB) and CNS colonization are unclear. Astrocytes are increasingly implicated in the pathogenesis of brain metastasis but in vitro work suggests both tumoricidal...

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Autores principales: O'Brien, Emma R., Howarth, Clare, Sibson, Nicola R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627137/
https://www.ncbi.nlm.nih.gov/pubmed/23596394
http://dx.doi.org/10.3389/fncel.2013.00040
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author O'Brien, Emma R.
Howarth, Clare
Sibson, Nicola R.
author_facet O'Brien, Emma R.
Howarth, Clare
Sibson, Nicola R.
author_sort O'Brien, Emma R.
collection PubMed
description Brain metastasis is a significant clinical problem, yet the mechanisms governing tumor cell extravasation across the blood-brain barrier (BBB) and CNS colonization are unclear. Astrocytes are increasingly implicated in the pathogenesis of brain metastasis but in vitro work suggests both tumoricidal and tumor-promoting roles for astrocyte-derived molecules. Also, the involvement of astrogliosis in primary brain tumor progression is under much investigation. However, translation of in vitro findings into in vivo and clinical settings has not been realized. Increasingly sophisticated resources, such as transgenic models and imaging technologies aimed at astrocyte-specific markers, will enable better characterization of astrocyte function in CNS tumors. Techniques such as bioluminescence and in vivo fluorescent cell labeling have potential for understanding the real-time responses of astrocytes to tumor burden. Transgenic models targeting signaling pathways involved in the astrocytic response also hold great promise, allowing translation of in vitro mechanistic findings into pre-clinical models. The challenging nature of in vivo CNS work has slowed progress in this area. Nonetheless, there has been a surge of interest in generating pre-clinical models, yielding insights into cell extravasation across the BBB, as well as immune cell recruitment to the parenchyma. While the function of astrocytes in the tumor microenvironment is still unknown, the relationship between astrogliosis and tumor growth is evident. Here, we review the role of astrogliosis in both primary and secondary brain tumors and outline the potential for the use of novel imaging modalities in research and clinical settings. These imaging approaches have the potential to enhance our understanding of the local host response to tumor progression in the brain, as well as providing new, more sensitive diagnostic imaging methods.
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spelling pubmed-36271372013-04-17 The role of astrocytes in CNS tumors: pre-clinical models and novel imaging approaches O'Brien, Emma R. Howarth, Clare Sibson, Nicola R. Front Cell Neurosci Neuroscience Brain metastasis is a significant clinical problem, yet the mechanisms governing tumor cell extravasation across the blood-brain barrier (BBB) and CNS colonization are unclear. Astrocytes are increasingly implicated in the pathogenesis of brain metastasis but in vitro work suggests both tumoricidal and tumor-promoting roles for astrocyte-derived molecules. Also, the involvement of astrogliosis in primary brain tumor progression is under much investigation. However, translation of in vitro findings into in vivo and clinical settings has not been realized. Increasingly sophisticated resources, such as transgenic models and imaging technologies aimed at astrocyte-specific markers, will enable better characterization of astrocyte function in CNS tumors. Techniques such as bioluminescence and in vivo fluorescent cell labeling have potential for understanding the real-time responses of astrocytes to tumor burden. Transgenic models targeting signaling pathways involved in the astrocytic response also hold great promise, allowing translation of in vitro mechanistic findings into pre-clinical models. The challenging nature of in vivo CNS work has slowed progress in this area. Nonetheless, there has been a surge of interest in generating pre-clinical models, yielding insights into cell extravasation across the BBB, as well as immune cell recruitment to the parenchyma. While the function of astrocytes in the tumor microenvironment is still unknown, the relationship between astrogliosis and tumor growth is evident. Here, we review the role of astrogliosis in both primary and secondary brain tumors and outline the potential for the use of novel imaging modalities in research and clinical settings. These imaging approaches have the potential to enhance our understanding of the local host response to tumor progression in the brain, as well as providing new, more sensitive diagnostic imaging methods. Frontiers Media S.A. 2013-04-16 /pmc/articles/PMC3627137/ /pubmed/23596394 http://dx.doi.org/10.3389/fncel.2013.00040 Text en Copyright © 2013 O'Brien, Howarth and Sibson. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
spellingShingle Neuroscience
O'Brien, Emma R.
Howarth, Clare
Sibson, Nicola R.
The role of astrocytes in CNS tumors: pre-clinical models and novel imaging approaches
title The role of astrocytes in CNS tumors: pre-clinical models and novel imaging approaches
title_full The role of astrocytes in CNS tumors: pre-clinical models and novel imaging approaches
title_fullStr The role of astrocytes in CNS tumors: pre-clinical models and novel imaging approaches
title_full_unstemmed The role of astrocytes in CNS tumors: pre-clinical models and novel imaging approaches
title_short The role of astrocytes in CNS tumors: pre-clinical models and novel imaging approaches
title_sort role of astrocytes in cns tumors: pre-clinical models and novel imaging approaches
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627137/
https://www.ncbi.nlm.nih.gov/pubmed/23596394
http://dx.doi.org/10.3389/fncel.2013.00040
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