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Intravital imaging of glioma border morphology reveals distinctive cellular dynamics and contribution to tumor cell invasion

The pathogenesis of glioblastoma (GBM) is characterized by highly invasive behavior allowing dissemination and progression. A conclusive image of the invasive process is not available. The aim of this work was to study invasion dynamics in GBM using an innovative in vivo imaging approach. Primary br...

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Autores principales: Alieva, Maria, Leidgens, Verena, Riemenschneider, Markus J., Klein, Christoph A., Hau, Peter, van Rheenen, Jacco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375955/
https://www.ncbi.nlm.nih.gov/pubmed/30765850
http://dx.doi.org/10.1038/s41598-019-38625-4
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author Alieva, Maria
Leidgens, Verena
Riemenschneider, Markus J.
Klein, Christoph A.
Hau, Peter
van Rheenen, Jacco
author_facet Alieva, Maria
Leidgens, Verena
Riemenschneider, Markus J.
Klein, Christoph A.
Hau, Peter
van Rheenen, Jacco
author_sort Alieva, Maria
collection PubMed
description The pathogenesis of glioblastoma (GBM) is characterized by highly invasive behavior allowing dissemination and progression. A conclusive image of the invasive process is not available. The aim of this work was to study invasion dynamics in GBM using an innovative in vivo imaging approach. Primary brain tumor initiating cell lines from IDH-wild type GBM stably expressing H2B-Dendra2 were implanted orthotopically in the brains of SCID mice. Using high-resolution time-lapse intravital imaging, tumor cell migration in the tumor core, border and invasive front was recorded. Tumor cell dynamics at different border configurations were analyzed and multivariate linear modelling of tumor cell spreading was performed. We found tumor border configurations, recapitulating human tumor border morphologies. Not only tumor borders but also the tumor core was composed of highly dynamic cells, with no clear correlation to the ability to spread into the brain. Two types of border configurations contributed to tumor cell spreading through distinct invasion patterns: an invasive margin that executes slow but directed invasion, and a diffuse infiltration margin with fast but less directed movement. By providing a more detailed view on glioma invasion patterns, our study may improve accuracy of prognosis and serve as a basis for personalized therapeutic approaches.
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spelling pubmed-63759552019-02-19 Intravital imaging of glioma border morphology reveals distinctive cellular dynamics and contribution to tumor cell invasion Alieva, Maria Leidgens, Verena Riemenschneider, Markus J. Klein, Christoph A. Hau, Peter van Rheenen, Jacco Sci Rep Article The pathogenesis of glioblastoma (GBM) is characterized by highly invasive behavior allowing dissemination and progression. A conclusive image of the invasive process is not available. The aim of this work was to study invasion dynamics in GBM using an innovative in vivo imaging approach. Primary brain tumor initiating cell lines from IDH-wild type GBM stably expressing H2B-Dendra2 were implanted orthotopically in the brains of SCID mice. Using high-resolution time-lapse intravital imaging, tumor cell migration in the tumor core, border and invasive front was recorded. Tumor cell dynamics at different border configurations were analyzed and multivariate linear modelling of tumor cell spreading was performed. We found tumor border configurations, recapitulating human tumor border morphologies. Not only tumor borders but also the tumor core was composed of highly dynamic cells, with no clear correlation to the ability to spread into the brain. Two types of border configurations contributed to tumor cell spreading through distinct invasion patterns: an invasive margin that executes slow but directed invasion, and a diffuse infiltration margin with fast but less directed movement. By providing a more detailed view on glioma invasion patterns, our study may improve accuracy of prognosis and serve as a basis for personalized therapeutic approaches. Nature Publishing Group UK 2019-02-14 /pmc/articles/PMC6375955/ /pubmed/30765850 http://dx.doi.org/10.1038/s41598-019-38625-4 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Alieva, Maria
Leidgens, Verena
Riemenschneider, Markus J.
Klein, Christoph A.
Hau, Peter
van Rheenen, Jacco
Intravital imaging of glioma border morphology reveals distinctive cellular dynamics and contribution to tumor cell invasion
title Intravital imaging of glioma border morphology reveals distinctive cellular dynamics and contribution to tumor cell invasion
title_full Intravital imaging of glioma border morphology reveals distinctive cellular dynamics and contribution to tumor cell invasion
title_fullStr Intravital imaging of glioma border morphology reveals distinctive cellular dynamics and contribution to tumor cell invasion
title_full_unstemmed Intravital imaging of glioma border morphology reveals distinctive cellular dynamics and contribution to tumor cell invasion
title_short Intravital imaging of glioma border morphology reveals distinctive cellular dynamics and contribution to tumor cell invasion
title_sort intravital imaging of glioma border morphology reveals distinctive cellular dynamics and contribution to tumor cell invasion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375955/
https://www.ncbi.nlm.nih.gov/pubmed/30765850
http://dx.doi.org/10.1038/s41598-019-38625-4
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