Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

On the translational axis from bench to bedside, it is important to have glioblastoma (GBM) models which closely reflect the clinical situation. Such models should be suitable for investigation of clinically relevant endpoints as well as reasonable regarding costs and feasible regarding statistically necessary animal numbers. Established cell lines are comprehensively characterized and can be efficiently engrafted in large cohorts of animals. In this project, a panel of five human GBM cell lines (U 87 MG, U 251 MG, A7, LN 229, HGL21) is characterized after subcutaneous and orthotopic xenograft transplantation (take rate, radiosensitivity, histology, putative stem cell markers (SM)) to investigate their potential as suitable GBM models.
Limiting dilution assays were performed using subcutaneous injection of decreasing cell numbers and take dose 50% (TD50) was low for the five GBM models. Intrinsic radiosensitivity and effectiveness of combined radiochemotherapy was studied by irradiation of subcutaneous tumors with different dose levels. Although high amounts of cancer initiating cells are indicated by the low TD50 values the surprisingly low tumor control dose 50% (TCD50) values are in contrast to the remarkable radioresistance of GBM in patients. Intracranial transplantation of mCherry- or luciferase-positive cell variants was performed with a stereotactic frame. Weekly optical imaging and contrast-enhanced magnetic resonance imaging revealed no tumor growth for one of four investigated models. After excision, tumors were analysed histologically (Haematoxylin/Eosin, SM). Three models grew within 30-60 days to end size but the histological phenotypes generally showed weak analogy to GBM patients. Although xenograft models from established cell lines of other entities very closely mirror the clinical situation, this remains questionable for GBM.