Abstract
INTRODUCTION: Glioblastoma Multiforme(GBM) is the most severe type of brain malignancy, the median survival doesn't exceed 15 months. 5-Aminolevulinic acid (5-ALA) induced fluorescent-guided surgery has resulted in a more complete resection recently. After intake, 5-ALA is converted into the fluorescing PPIX, preferentially accumulating in GBM. The tumour margin is defined by lack of fluorescence, tumour cells within seem to display traits different from the mass. To gain a better understanding of these cells might prove beneficial for future therapies. Thus, we investigated differences in expression, growth and tumourigenicity in surgical specimen and patient-derived cell lines. METHOD: To investigate if there are cells other than tumour fluorescing, surgical specimen from mass and margin were subjected to flow cytometry. To be able to derive cell lines from the margin, the Cambridge protocol (Fael Al Mayhani 2009) was subjected to some changes. Next, surgical specimen and cell lines from mass and margin were analysed with regard to their expression of markers related to cell type, vascularisation, proliferation and resistance. RESULTS: Flow cytometry and analysis of different markers might point fluorescence being restricted to tumour cells. A protocol for derivation of margin derived cell lines could be generated successfully. Surgical specimen and patient derived cell lines from the margin of GBM showed a higher expression of SOX2, decreased proliferation and tumorigenicity and a trend towards higher resistance in vitro. CONCLUSION: Tumour cells residing in the margin might possess a quiescent phenotype and higher resistance. Thusly, it might be interesting to find a way to sensitise cells to conventional therapy.
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