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ADAMTS1 Supports Endothelial Plasticity of Glioblastoma Cells with Relevance for Glioma Progression

Gliomas in general and the more advanced glioblastomas (GBM) in particular are the most usual tumors of the central nervous system with poor prognosis. GBM patients develop resistance to distinct therapies, in part due to the existence of tumor cell subpopulations with stem-like properties that part...

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Autores principales: Serrano-Garrido, Orlando, Peris-Torres, Carlos, Redondo-García, Silvia, Asenjo, Helena G., Plaza-Calonge, María del Carmen, Fernandez-Luna, José Luis, Rodríguez-Manzaneque, Juan Carlos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823850/
https://www.ncbi.nlm.nih.gov/pubmed/33396280
http://dx.doi.org/10.3390/biom11010044
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author Serrano-Garrido, Orlando
Peris-Torres, Carlos
Redondo-García, Silvia
Asenjo, Helena G.
Plaza-Calonge, María del Carmen
Fernandez-Luna, José Luis
Rodríguez-Manzaneque, Juan Carlos
author_facet Serrano-Garrido, Orlando
Peris-Torres, Carlos
Redondo-García, Silvia
Asenjo, Helena G.
Plaza-Calonge, María del Carmen
Fernandez-Luna, José Luis
Rodríguez-Manzaneque, Juan Carlos
author_sort Serrano-Garrido, Orlando
collection PubMed
description Gliomas in general and the more advanced glioblastomas (GBM) in particular are the most usual tumors of the central nervous system with poor prognosis. GBM patients develop resistance to distinct therapies, in part due to the existence of tumor cell subpopulations with stem-like properties that participate in trans-differentiation events. Within the complex tumor microenvironment, the involvement of extracellular proteases remains poorly understood. The extracellular protease ADAMTS1 has already been reported to contribute to the plasticity of cancer cells. Accordingly, this basic knowledge and the current availability of massive sequencing data from human gliomas, reinforced the development of this work. We first performed an in silico study of ADAMTS1 and endothelial markers in human gliomas, providing the basis to further assess these molecules in several primary glioblastoma-initiating cells and established GBM cells with the ability to acquire an endothelial-like phenotype. Using a co-culture approach of endothelial and GBM cells, we noticed a relevant function of ADAMTS1 in GBM cells leading the organization of endothelial-like networks and, even more significantly, we found a blockade of the formation of tumor-spheres and a deficient response to hypoxia in the absence of ADAMTS1. Our data support a chief role of this protease modulating the phenotypic plasticity of GBM.
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spelling pubmed-78238502021-01-24 ADAMTS1 Supports Endothelial Plasticity of Glioblastoma Cells with Relevance for Glioma Progression Serrano-Garrido, Orlando Peris-Torres, Carlos Redondo-García, Silvia Asenjo, Helena G. Plaza-Calonge, María del Carmen Fernandez-Luna, José Luis Rodríguez-Manzaneque, Juan Carlos Biomolecules Article Gliomas in general and the more advanced glioblastomas (GBM) in particular are the most usual tumors of the central nervous system with poor prognosis. GBM patients develop resistance to distinct therapies, in part due to the existence of tumor cell subpopulations with stem-like properties that participate in trans-differentiation events. Within the complex tumor microenvironment, the involvement of extracellular proteases remains poorly understood. The extracellular protease ADAMTS1 has already been reported to contribute to the plasticity of cancer cells. Accordingly, this basic knowledge and the current availability of massive sequencing data from human gliomas, reinforced the development of this work. We first performed an in silico study of ADAMTS1 and endothelial markers in human gliomas, providing the basis to further assess these molecules in several primary glioblastoma-initiating cells and established GBM cells with the ability to acquire an endothelial-like phenotype. Using a co-culture approach of endothelial and GBM cells, we noticed a relevant function of ADAMTS1 in GBM cells leading the organization of endothelial-like networks and, even more significantly, we found a blockade of the formation of tumor-spheres and a deficient response to hypoxia in the absence of ADAMTS1. Our data support a chief role of this protease modulating the phenotypic plasticity of GBM. MDPI 2020-12-31 /pmc/articles/PMC7823850/ /pubmed/33396280 http://dx.doi.org/10.3390/biom11010044 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Serrano-Garrido, Orlando
Peris-Torres, Carlos
Redondo-García, Silvia
Asenjo, Helena G.
Plaza-Calonge, María del Carmen
Fernandez-Luna, José Luis
Rodríguez-Manzaneque, Juan Carlos
ADAMTS1 Supports Endothelial Plasticity of Glioblastoma Cells with Relevance for Glioma Progression
title ADAMTS1 Supports Endothelial Plasticity of Glioblastoma Cells with Relevance for Glioma Progression
title_full ADAMTS1 Supports Endothelial Plasticity of Glioblastoma Cells with Relevance for Glioma Progression
title_fullStr ADAMTS1 Supports Endothelial Plasticity of Glioblastoma Cells with Relevance for Glioma Progression
title_full_unstemmed ADAMTS1 Supports Endothelial Plasticity of Glioblastoma Cells with Relevance for Glioma Progression
title_short ADAMTS1 Supports Endothelial Plasticity of Glioblastoma Cells with Relevance for Glioma Progression
title_sort adamts1 supports endothelial plasticity of glioblastoma cells with relevance for glioma progression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823850/
https://www.ncbi.nlm.nih.gov/pubmed/33396280
http://dx.doi.org/10.3390/biom11010044
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