Astrocytoma cell lines transduced to either express GFAP isoforms or to knockdown GFAP isoforms

Modulation of the GFAP cytoskeleton in astrocytoma cells alters processes involved in extracellular matrix remodelling and cell-cell signalling – a transcriptome analysis Astrocytomas grade IV are malignant brain tumours with no effective treatment and a five year survival rate of only 5%. Expression of Glial Fibrillary Acidic Protein (GFAP) is lower in high astrocytoma grade, but the expression of the splice isoform GFAPδ is similar in low and high-grade astrocytomas. Thus the ratio of GFAPδ/α is increased in high-grade astrocytomas. We studied transcriptome changes in astrocytoma cell lines resulting from an induced alteration of GFAP isoform expression. GFAPα or GFAPδ were increased or decreased by recombinant expression or shRNA mediated knockdown of GFAPpan or GFAPα. We find that the most prominent effects are induced by the modulations where the GFAPδ/GFAPα ratio is increased. Gene ontology analysis revealed that the main effects of GFAP modulation take place in the extracellular matrix remodelling and cellular signalling clusters, with possible implications in astrocytoma invasive behaviour and angiogenesis. 2 cell lines (U251 and U373) with respectively recombinant expression or knockdown of GFAP isoforms. Biological replicates: U251 control - N=8, U251 recombinant GFAPa - N=8, U251 Recombinant GFAPdelta - N=8, U373 shRNA Non Targeting Control - N=6, U373 shRNA GFAPalpha - N=5, U373 shRNA GFAPpan - N=5