Serrano-Garrido, OrlandoPeris-Torres, CarlosRedondo-García, SilviaAsenjo, Helena G.Plaza-Calonge, María del CarmenFernandez-Luna, José LuisRodríguez-Manzaneque, Juan Carlos2022-10-052022-10-052020-12-31Serrano-Garrido O, Peris-Torres C, Redondo-García S, Asenjo HG, Plaza-Calonge MDC, Fernandez-Luna JL, et al. ADAMTS1 Supports Endothelial Plasticity of Glioblastoma Cells with Relevance for Glioma Progression. Biomolecules. 2020 Dec 31;11(1):44http://hdl.handle.net/10668/4225Gliomas 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/ADAMTS proteasesEndothelial-like phenotypeExtracellular metalloproteaseGlioblastomaPlasticityTumor microenvironmentCell lineEndothelial cellsGliomaProteínas ADAMTSFenotipoMetaloproteasasMatriz extracelularPlasticidad de la célulaMicroambiente tumoralLínea celularCélulas endotelialesMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, TumorMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease ProgressionMedical Subject Headings::Anatomy::Cells::Epithelial Cells::Endothelial CellsMedical Subject Headings::Check Tags::FemaleGene Expression Regulation, NeoplasticMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Neoplasms, Neuroepithelial::Glioma::Astrocytoma::GlioblastomaMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neoplasms, Neuroepithelial::GliomaMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Anatomy::Cells::Stem Cells::Neoplastic Stem CellsMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cellular Microenvironment::Tumor MicroenvironmentMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Culture Techniques::Coculture TechniquesMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::PhenotypeMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::Adaptation, PhysiologicalMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell TransdifferentiationMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::PrognosisMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide HydrolasesMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Nervous System Neoplasms::Central Nervous System Neoplasms::Brain Neoplasmsresearch article33396280Acceso abierto10.3390/biom110100442218-273XPMC7823850