gms | German Medical Science

Objective: Malignant brain tumours possess a hierarchy of cells differing in tumorigenic potential. Among the heterogeneous cell populations within the malignant glioma, so called Brain Tumour Initiating Cells (BTICs) are thought to be the most tumorigenic cellular compartment capable of re-populating the entire spectrum of morpho- and histotypes characteristic to GBM. There is an urgent need for adequate models that would recapitulate the hallmark features of BTICs. The aim of this study was to characterize a panel of glioma cell lines with respect to the phenotypic and biological features characteristic for BTICs.

Methods: Neurosphere cultures of 10 established cell lines were propagated under serum-free conditions. The tumorigenic potential of neurospheres was evaluated in an orthotopic glioma mouse model. Histological and immunohistochemical characterization was performed on formalin-fixed, paraffin-embedded tissue samples. For local radiation therapy, mice bearing implanted glioma neurospheres were anesthetised and subjected to fractionated radiation with 6x2,5 Gy over 6 days.

Results: A panel of ten glioma cell lines was characterized with respect to the BTICs phenotype in vitro and in vivo. Glioma cell lines can be categorized based on the extent to which they recapitulate properties of BTICs. Out of ten lines, three (30%) showed the propensity to generate long-term neurosphere culture properties. Out of three neurosphere-forming lines, two gave rise to tumours with invasive phenotype and one possessed the propensity for phenotypic differentiation. Interestingly, the phenotypic plasticity correlates with the invasive tumour phenotype and poor response to radiotherapy (P>0,05). In contrast to previous reports, no correlation between CD133 expression and BTIC phenotype was found.

Conclusions: Long-term tissue culture under serum containing conditions per se does not irradicate BTICs from glioma cell lines. However, a serum-based condition may select non-BTIC glioma cell populations, which are more abundant than BTICs. Similar to the cellular hierarchy in GBM, there is a hierarchy in glioma cell lines, of which some may be derived from BTICs.