Quantitative Proteomics Reveals Metabolic Differences in Homing and Non-Homing Glioma Stem Cell Xenografts and Stromal Cells

ABSTRACT: Glioblastoma is the most common and most devastating adult primary brain tumor. Despite aggressive multimodal therapy, the median survival is approximately one year after diagnosis. In recent years bone marrow-derived human mesenchymal stem cells (BM-hMSCs) have shown promise as cell-based delivery vehicles for anti-glioma therapeutics. This is largely due to their innate ability to migrate towards gliomas. Several studies have successfully demonstrated their use as delivery vehicles for anti-glioma agents. However, it is now evident that BM-hMSCs demonstrate variable tropism towards gliomas based on a clinically relevant glioma stem cell (GSC) model of GBM. In this study, we compared the proteomic profile of cancer and stromal cell populations in GSC xenografts that attract BM-hMSCs (‘attractors’) with those to do not (‘non-attractors’) in order to identify cell-signaling pathways that may modulate BM-hMSCs homing followed by targeted transcriptomic analysis of human gene sets related to glioma biology. We identified lower protein expression of fatty acid metabolism and glucose-dependent metabolic pathways in attractors. While transcriptomic analysis suggested that N-linked glycosylation was increased. Conversely, glucose metabolic pathways, including oxidative phosphorylation, were increased in the stromal cells present in attractors. The results presented here provide the first evidence for glucose metabolism, reactive oxidative species and lipid-mediated tumor inflammatory response, and N-linked glycosylation in the homing of BM-hMSC to GSC xenografts. Reciprocal expression of these pathways in the stromal cell population may suggest microenvironment cross-talk. Our studies provide new insights on the signaling correlates underlying the differential homing capacity of BM-hMSCs to GSC xenografts.

OTHER RELATED OMICS DATASETS IN: MODEL1109130000 MODEL1909260003 MODEL1909260004 MODEL1703310000 MODEL1909260005 MODEL1909260006 MODEL1311110000 MODEL1311110001

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human) Homo Sapiens/mus Musculus Xenograft Mus Musculus (mouse)

TISSUE(S): Brain

DISEASE(S): Glioblastoma,Brain Cancer

SUBMITTER: Norelle Wildburger  

LAB HEAD: Carol L. Nilsson

PROVIDER: PXD001778 | Pride | 2016-02-17

REPOSITORIES: Pride