P01.01.A CHARACTERIZATION OF GLIOBLASTOMA’S MIGRATION HETEROGENEITY THROUGH A PATIENT-DERIVED 3D MODEL

P01.01.A CHARACTERIZATION OF GLIOBLASTOMA’S MIGRATION HETEROGENEITY THROUGH A PATIENT-DERIVED 3D MODEL

Abstract BACKGROUND Glioblastoma (GB) is an aggressive brain cancer with an average survival of 14.6 months. Effective treatment is hindered by GB’s plasticity and invasive phenotype. Little is known regarding the molecular mechanisms driving invasion heterogeneity. MATERIAL AND METHODS We developed...

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Veröffentlicht in:Neuro-oncology (Charlottesville, Va.) Va.), 2024-10, Vol.26 (Supplement_5), p.v30-v30
Hauptverfasser: Pujol-Castiblanque, A, Savin, T, Markaki, A E, Mair, R
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container_title Neuro-oncology (Charlottesville, Va.)
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creator Pujol-Castiblanque, A
Savin, T
Markaki, A E
Mair, R
description Abstract BACKGROUND Glioblastoma (GB) is an aggressive brain cancer with an average survival of 14.6 months. Effective treatment is hindered by GB’s plasticity and invasive phenotype. Little is known regarding the molecular mechanisms driving invasion heterogeneity. MATERIAL AND METHODS We developed a bioengineered model of brain-like matrix, which together with patient-derived spheroids, allows study of GB’s migration in vitro. Twenty patient-derived cell lines with different intrinsic (genomic, transcriptomic) characteristics in several extrinsic (extracellular matrix stiffness, hypoxia vs normoxia) conditions were tested. RESULTS Time-lapse video analysis identified recurrent migratory phenotypes across the cell lines. GB’s subtype- proneural, neural, classical, and mesenchymal- did not cluster cell lines with similar migratory phenotypes. An increase in matrix stiffness led to a switch in migratory phenotype in certain cell lines. CONCLUSION We have identified finite and periodic migration phenotypes of GB in different conditions.
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Effective treatment is hindered by GB’s plasticity and invasive phenotype. Little is known regarding the molecular mechanisms driving invasion heterogeneity. MATERIAL AND METHODS We developed a bioengineered model of brain-like matrix, which together with patient-derived spheroids, allows study of GB’s migration in vitro. Twenty patient-derived cell lines with different intrinsic (genomic, transcriptomic) characteristics in several extrinsic (extracellular matrix stiffness, hypoxia vs normoxia) conditions were tested. RESULTS Time-lapse video analysis identified recurrent migratory phenotypes across the cell lines. GB’s subtype- proneural, neural, classical, and mesenchymal- did not cluster cell lines with similar migratory phenotypes. An increase in matrix stiffness led to a switch in migratory phenotype in certain cell lines. 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Effective treatment is hindered by GB’s plasticity and invasive phenotype. Little is known regarding the molecular mechanisms driving invasion heterogeneity. MATERIAL AND METHODS We developed a bioengineered model of brain-like matrix, which together with patient-derived spheroids, allows study of GB’s migration in vitro. Twenty patient-derived cell lines with different intrinsic (genomic, transcriptomic) characteristics in several extrinsic (extracellular matrix stiffness, hypoxia vs normoxia) conditions were tested. RESULTS Time-lapse video analysis identified recurrent migratory phenotypes across the cell lines. GB’s subtype- proneural, neural, classical, and mesenchymal- did not cluster cell lines with similar migratory phenotypes. An increase in matrix stiffness led to a switch in migratory phenotype in certain cell lines. 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title P01.01.A CHARACTERIZATION OF GLIOBLASTOMA’S MIGRATION HETEROGENEITY THROUGH A PATIENT-DERIVED 3D MODEL
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