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Spatiotemporal analysis of glioma heterogeneity reveals COL1A1 as an actionable target to disrupt tumor progression

Intra-tumoral heterogeneity is a hallmark of glioblastoma that challenges treatment efficacy. However, the mechanisms that set up tumor heterogeneity and tumor cell migration remain poorly understood. Herein, we present a comprehensive spatiotemporal study that aligns distinctive intra-tumoral histo...

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Autores principales: Comba, Andrea, Faisal, Syed M., Dunn, Patrick J., Argento, Anna E., Hollon, Todd C., Al-Holou, Wajd N., Varela, Maria Luisa, Zamler, Daniel B., Quass, Gunnar L., Apostolides, Pierre F., Abel, Clifford, Brown, Christine E., Kish, Phillip E., Kahana, Alon, Kleer, Celina G., Motsch, Sebastien, Castro, Maria G., Lowenstein, Pedro R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9232499/
https://www.ncbi.nlm.nih.gov/pubmed/35750880
http://dx.doi.org/10.1038/s41467-022-31340-1
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author Comba, Andrea
Faisal, Syed M.
Dunn, Patrick J.
Argento, Anna E.
Hollon, Todd C.
Al-Holou, Wajd N.
Varela, Maria Luisa
Zamler, Daniel B.
Quass, Gunnar L.
Apostolides, Pierre F.
Abel, Clifford
Brown, Christine E.
Kish, Phillip E.
Kahana, Alon
Kleer, Celina G.
Motsch, Sebastien
Castro, Maria G.
Lowenstein, Pedro R.
author_facet Comba, Andrea
Faisal, Syed M.
Dunn, Patrick J.
Argento, Anna E.
Hollon, Todd C.
Al-Holou, Wajd N.
Varela, Maria Luisa
Zamler, Daniel B.
Quass, Gunnar L.
Apostolides, Pierre F.
Abel, Clifford
Brown, Christine E.
Kish, Phillip E.
Kahana, Alon
Kleer, Celina G.
Motsch, Sebastien
Castro, Maria G.
Lowenstein, Pedro R.
author_sort Comba, Andrea
collection PubMed
description Intra-tumoral heterogeneity is a hallmark of glioblastoma that challenges treatment efficacy. However, the mechanisms that set up tumor heterogeneity and tumor cell migration remain poorly understood. Herein, we present a comprehensive spatiotemporal study that aligns distinctive intra-tumoral histopathological structures, oncostreams, with dynamic properties and a specific, actionable, spatial transcriptomic signature. Oncostreams are dynamic multicellular fascicles of spindle-like and aligned cells with mesenchymal properties, detected using ex vivo explants and in vivo intravital imaging. Their density correlates with tumor aggressiveness in genetically engineered mouse glioma models, and high grade human gliomas. Oncostreams facilitate the intra-tumoral distribution of tumoral and non-tumoral cells, and potentially the collective invasion of the normal brain. These fascicles are defined by a specific molecular signature that regulates their organization and function. Oncostreams structure and function depend on overexpression of COL1A1. Col1a1 is a central gene in the dynamic organization of glioma mesenchymal transformation, and a powerful regulator of glioma malignant behavior. Inhibition of Col1a1 eliminates oncostreams, reprograms the malignant histopathological phenotype, reduces expression of the mesenchymal associated genes, induces changes in the tumor microenvironment and prolongs animal survival. Oncostreams represent a pathological marker of potential value for diagnosis, prognosis, and treatment.
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spelling pubmed-92324992022-06-26 Spatiotemporal analysis of glioma heterogeneity reveals COL1A1 as an actionable target to disrupt tumor progression Comba, Andrea Faisal, Syed M. Dunn, Patrick J. Argento, Anna E. Hollon, Todd C. Al-Holou, Wajd N. Varela, Maria Luisa Zamler, Daniel B. Quass, Gunnar L. Apostolides, Pierre F. Abel, Clifford Brown, Christine E. Kish, Phillip E. Kahana, Alon Kleer, Celina G. Motsch, Sebastien Castro, Maria G. Lowenstein, Pedro R. Nat Commun Article Intra-tumoral heterogeneity is a hallmark of glioblastoma that challenges treatment efficacy. However, the mechanisms that set up tumor heterogeneity and tumor cell migration remain poorly understood. Herein, we present a comprehensive spatiotemporal study that aligns distinctive intra-tumoral histopathological structures, oncostreams, with dynamic properties and a specific, actionable, spatial transcriptomic signature. Oncostreams are dynamic multicellular fascicles of spindle-like and aligned cells with mesenchymal properties, detected using ex vivo explants and in vivo intravital imaging. Their density correlates with tumor aggressiveness in genetically engineered mouse glioma models, and high grade human gliomas. Oncostreams facilitate the intra-tumoral distribution of tumoral and non-tumoral cells, and potentially the collective invasion of the normal brain. These fascicles are defined by a specific molecular signature that regulates their organization and function. Oncostreams structure and function depend on overexpression of COL1A1. Col1a1 is a central gene in the dynamic organization of glioma mesenchymal transformation, and a powerful regulator of glioma malignant behavior. Inhibition of Col1a1 eliminates oncostreams, reprograms the malignant histopathological phenotype, reduces expression of the mesenchymal associated genes, induces changes in the tumor microenvironment and prolongs animal survival. Oncostreams represent a pathological marker of potential value for diagnosis, prognosis, and treatment. Nature Publishing Group UK 2022-06-24 /pmc/articles/PMC9232499/ /pubmed/35750880 http://dx.doi.org/10.1038/s41467-022-31340-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Comba, Andrea
Faisal, Syed M.
Dunn, Patrick J.
Argento, Anna E.
Hollon, Todd C.
Al-Holou, Wajd N.
Varela, Maria Luisa
Zamler, Daniel B.
Quass, Gunnar L.
Apostolides, Pierre F.
Abel, Clifford
Brown, Christine E.
Kish, Phillip E.
Kahana, Alon
Kleer, Celina G.
Motsch, Sebastien
Castro, Maria G.
Lowenstein, Pedro R.
Spatiotemporal analysis of glioma heterogeneity reveals COL1A1 as an actionable target to disrupt tumor progression
title Spatiotemporal analysis of glioma heterogeneity reveals COL1A1 as an actionable target to disrupt tumor progression
title_full Spatiotemporal analysis of glioma heterogeneity reveals COL1A1 as an actionable target to disrupt tumor progression
title_fullStr Spatiotemporal analysis of glioma heterogeneity reveals COL1A1 as an actionable target to disrupt tumor progression
title_full_unstemmed Spatiotemporal analysis of glioma heterogeneity reveals COL1A1 as an actionable target to disrupt tumor progression
title_short Spatiotemporal analysis of glioma heterogeneity reveals COL1A1 as an actionable target to disrupt tumor progression
title_sort spatiotemporal analysis of glioma heterogeneity reveals col1a1 as an actionable target to disrupt tumor progression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9232499/
https://www.ncbi.nlm.nih.gov/pubmed/35750880
http://dx.doi.org/10.1038/s41467-022-31340-1
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