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

Alieva, Maria and Leidgens, Verena and Riemenschneider, Markus J. and Klein, Christoph A. and Hau, Peter and van Rheenen, Jacco (2019) Intravital imaging of glioma border morphology reveals distinctive cellular dynamics and contribution to tumor cell invasion. SCIENTIFIC REPORTS, 9: 2054. ISSN 2045-2322,

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: CANCER STEM-CELLS; BRAIN EXTRACELLULAR-MATRIX; COLLECTIVE INVASION; DIFFUSE GLIOMA; GLIOBLASTOMA; MIGRATION; MECHANISMS; IDENTIFICATION; TEMOZOLOMIDE; PLASTICITY;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Neurologie
Medicine > Abteilung für Neuropathologie
Medicine > Zentren des Universitätsklinikums Regensburg > Zentrum für Hirntumore (ZHT)
Medicine > Lehrstuhl für experimentelle Medizin und Therapieverfahren
Depositing User: Dr. Gernot Deinzer
Date Deposited: 22 Apr 2020 04:41
Last Modified: 22 Apr 2020 04:41
URI: https://pred.uni-regensburg.de/id/eprint/27547

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