Identification of intrinsic in vitro cellular mechanisms for glioma invasion

Journal of Theoretical Biology
Marco TektonidisAndreas Deutsch

Abstract

Invasion of malignant glioma is a highly complex phenomenon involving molecular and cellular processes at various spatio-temporal scales, whose precise interplay is still not fully understood. In order to identify the intrinsic cellular mechanisms of glioma invasion, we study an in vitro culture of glioma cells. By means of a computational approach, based on a cellular automaton model, we compare simulation results to the experimental data and deduce cellular mechanisms from microscopic and macroscopic observables (experimental data). For the first time, it is shown that the migration/proliferation dichotomy plays a central role in the invasion of glioma cells. Interestingly, we conclude that a diverging invasive zone is a consequence of this dichotomy. Additionally, we observe that radial persistence of glioma cells in the vicinity of dense areas accelerates the invasion process. We argue that this persistence results from a cell-cell repulsion mechanism. If glioma cell behavior is regulated through a migration/proliferation dichotomy and a self-repellent mechanism, our simulations faithfully reproduce all the experimental observations.

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Related Concepts

Brain Tumor, Recurrent
Cell Motility
Mixed Gliomas
Neoplasm Invasiveness
Tumor Cells, Cultured
Spheroids, Cellular
Cell Proliferation
Malignant Neoplasms
Glioma
Microscopy

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