EXPLORING LOW-DENSITY LIPOPROTEIN RECEPTOR (LDLR) FAMILY IN GLIOBLASTOMA

Abstract

AIMS Cancer and neurodegenerative disease are unlikely to co-exist in the same patient. As glioblastoma is the most prevalent primary brain cancer, our research group is exploring how GBM is affected by genes implicated in Alzheimer’s disease. SorL1 has been established to be an important risk factor for Alzheimer’s disease and our group have shown it to be upregulated in patient derived GBM cells and it contributes to GBM cell migration and proliferation. SorL1 is part of a wider family of low-density lipoprotein receptor (LDLR) family and so my project was to explore the wider family as a potential target for investigation. METHOD The LDLR family were initially investigated using the bioinformatic data bases Xena browser and ivy Glioblastoma Atlas Project (ivyGAP). Xena browser reports RNA expression between healthy tissue samples (GTEX study) and from low grade glioma and glioblastoma and survival analysis while ivyGAP reports gene expression in the different anatomical regions of glioblastoma tumours. RESULTS Following bioinformatics and literature review: LRP1B, LRP5, LRP10 and Sortilin were chosen for further investigation. Western blot and immunocytochemistry were used to explore expression in cell lines SVGP12, U87MG and 1321N1. Sortilin and LRP10 were shown to be down regulated whilst LRP5 showed no significant differences between cell lines. CONCLUSION The next step in this project is to explore expression of the LRP family in patient derived cells and normal human astrocytes. As the expression of the LDLR family was region specific across the tumour (ivyGAP data) future work in the project will explore expression in 3D spheroids and organotypic brain slice cultures, to create a model that better recapitulates the tumour microenvironment to better understand these proteins and their roles in GBM