Proteomics

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Glioma initiating/stem cells, differentiation, iTRAQ analysis by QSTAR Elite


ABSTRACT: Glioma initiating/stem cells (GIC/GSC) are considered responsible for the therapeutic resistance and recurrence of malignant glioma. To clarify the molecular mechanism of GIC/GSC maintenance/differentiation, we established GIC/GSC clones, having the potential to differentiate into malignant gliomas, from glioblastoma patient’s tissues, and subjected to DNA microarray/iTRAQ based integrated proteomics. 21,857 mRNAs and 8,471 proteins were identified and integrated into a gene/protein expression analysis chart (iPEACH). The data integration and extraction of global proteins and mRNAs revealed that, during the GIC/GSC differentiation, cell adhesion molecules including integrin aV/ECMs and RAS-MAPK/PI3K signalings were significantly up-regulated, meanwhile, SOX2, CD133, and specific proteoglycans/synthetic-enzymes/metabolic pathways were obviously down-regulated. Among them, we focused proteoglycans and their synthetic-enzymes. GIC/GSC differentiation was significantly associated with the decrease of CSPG (CS-modified form) and dramatically induced by the CS-degradation enzyme which also induces the up-regulation of ERK-AKT signaling and GFAP without any other agents. Importantly, these differentiation processes were also associated with the interaction of CSPG (CS-unmodified form) and integrin-aV, and suppressed by integrin-inhibitors/CS administrations significantly. Combination treatments of a cancer-drug Temozolomide and these GIC/GSC-differentiation inhibitors suppressed glioma progression, increased the chemosensitivities, and led the longer survival of mouse xenograft-models. Functional integrated proteomics for the first time demonstrates that the GIC/GSC induces the specific proteoglycans to regulate GIC/GSC stemness/differentiation via the integlin signalings which may be a clinical target against malignant gliomas.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Norie Araki 

PROVIDER: PXD008332 | JPOST Repository | Fri Nov 30 00:00:00 GMT 2018

REPOSITORIES: jPOST

Dataset's files

Source:
Action DRS
Data100930_GSC_D5_025-240min-7.wiff Wiff
Data100930_GSC_D5_05-240min-9.wiff Wiff
Data101011_GSC_D4_025-110min-1.wiff Wiff
Data101011_GSC_D4_025-110min-2.wiff Wiff
Data101013_GSC_D4_025-110min-6.wiff Wiff
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