Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Glioma-initiating cells at tumor edge gain signals from tumor core cells to promote their malignancy

ABSTRACT: Intratumor spatial heterogeneity facilitates therapeutic resistance in glioblastoma (GBM). Nonetheless, understanding of GBM is limited to the resectable tumor core lesion while the seeds for recurrence reside in the unresectable tumor edge. In this study, stratification of GBM to core and edge demonstrated clinically relevant surgical sequelae. We establish regionally derived models of GBM edge and core that retain their spatial identity in a cell autonomous manner. Edge cells show a higher capacity for infiltrative growth, while core cells demonstrate greater therapy resistance. Investigation of intercellular signaling between these two cell populations uncovered the paracrine crosstalk from tumor core that provokes malignancy and therapy resistance of edge cells. These phenotypic alterations were initiated by HDAC1 in GBM core cells which subsequently affect edge cells by secreting the soluble form of CD109 protein. Our data reveal the role of intracellular communication between regionally different populations of GBM cells in tumor recurrence.

ORGANISM(S): Homo sapiens

PROVIDER: GSE153746 | GEO | 2020/07/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Crosstalk with astrocytes establishes tumor edge in glioblastoma

Project description:Clinical outcomes for patients with glioblastoma (GBM) are extremely poor due to inevitable tumor recurrence even after extensive treatments. These recurrences are thought to manifest from cells located within the tumor edge. Despite this, the precise molecular mechanism governing GBM spatial phenotypic heterogeneity (e.g. edge vs. core) and subsequent tumor recurrence remains poorly elucidated. Here, using patient-derived GBM core and edge tissues, we analyzed transcriptional and metabolic signatures in an effort to determine how GBM facilitates the edge phenotype and its associated recurrence-initiating cells (RICs). In so doing, we unexpectedly identified CD38 as an essential protein in the formation of the edge phenotype and found a CD38-driven interaction between edge GBM cells and neighboring astrocytes that communally develops a GBM edge that is unresectable by surgery and retains RICs.

2021-12-25 | GSE135408 | GEO

An anatomic proteomic atlas of human glioblastoma

Project description:Glioblastoma (GBM) is an aggressive form of brain cancer with well-established patterns of intra-tumoral heterogeneity implicated in treatment resistance, recurrence and progression. While the regional and single cell-level genetic variation of GBM have been recently resolved, downstream phenotype-level proteomic programs have yet to be assigned to specific niches. Here, we leverage laser capture microdissection and mass spectrometry-based proteomics to assign 4794 proteins to GBM’s hallmark histomorphologic niches across 20 patients. Importantly, this analysis defined 1360 regionally enriched proteins, including 502 which are proteogenomically concordant. We validate a subset of identified niche-specific markers using orthogonal immunohistochemical approaches and make the associated atlas publicly available as an online resource (https://www.brainproteinatlas.org/dash/apps/GPA). Spatial resolution of the molecular landscape of GBM, operational at the protein level, aims to further facilitate and refine our biological understanding and treatment approaches for this aggressive disease.

2021-11-02 | PXD019381 | Pride

Multi-omic screening of invasive GBM cells in engineered biomaterials and patient biopsies reveals targetable transsulfuration pathway alterations

Project description:Metabolic gene expression analysis of Glioblastoma cells from patient tumors edge vs core and the GBM cells from the edge and core of the 3d invasion model was carried out using Nanostring N counter platform

2023-12-01 | GSE246697 | GEO

Effect of the different isoforms of RPL22L1 protein on the transcriptome of human glioblastoma cells.

Project description:Glioblastoma multiforme (GBM) is characterized by an exceptionally high intratumoral heterogeneity. However, the molecular mechanisms underlying the origin of different GBM cell populations remain unclear. Here we found that the composition of ribosomes of GBM cells in the tumor core and edge differ due to alternative RNA splicing. The acidic pH in the core switches pre-mRNA splicing of the ribosomal gene RPL22L1 toward the RPL22L1b isoform. This allows cells to survive acidosis, increases stemness and correlates with worse patient outcome. Mechanistically, RPL22L1b promotes RNA splicing by binding to lncMALAT1 in the nucleus, resulting in its degradation. Contrarily, in the tumor edge region, RPL22L1a interacts with ribosomes in cytoplasm and upregulates translation of multiple mRNAs including TP53. We found that RPL22L1 isoform switch is regulated by SRSF4 and identified the compound, that inhibits this process and decreases tumor growth. These findings demonstrate how distinct GBM cell populations arise during tumor growth. Targeting this mechanism may decrease GBM heterogeneity and facilitate therapy.

2021-12-01 | GSE180465 | GEO

Interactome of different isoforms of RPL22L1 protein in human glioblastoma cells

2021-12-01 | GSE180464 | GEO

LC-MS/MS identification of proteins that were co-purified with Fc-tagged isoforms of RPL22L1

Project description:Glioblastoma (GBM) is characterized by an exceptionally high intratumoral heterogeneity. However, the molecular mechanisms underlying the origin of different GBM cell populations remain unclear. Here we found that the composition of ribosomes of GBM cells in the tumor core and edge differ due to alternative RNA splicing. The acidic pH in the core switches pre-mRNA splicing of the ribosomal gene RPL22L1 toward the RPL22L1b isoform. To elucidate the functions of RPL22L1 isoforms we identified proteins that interact with RPL22L1a and RPL22L1b. First, we generated GBM cells with stable expression of Fc-tagged RPL22L1 isoforms. Fc-RPL22L1a and Fc-RPL22L1b together with their binding partners were isolated from neurospheres using magnetic beads and analyzed by LC-MS/MS.

2023-10-24 | PXD035767 | Pride

LC-MS/MS identification of proteins that were bound to recombinant His-tagged isoforms of RPL22L1

Project description:Glioblastoma (GBM) is characterized by an exceptionally high intratumoral heterogeneity. However, the molecular mechanisms underlying the origin of different GBM cell populations remain unclear. Here we found that the composition of ribosomes of GBM cells in the tumor core and edge differ due to alternative RNA splicing. The acidic pH in the core switches pre-mRNA splicing of the ribosomal gene RPL22L1 toward the RPL22L1b isoform. To elucidate the functions of RPL22L1 isoforms we identified proteins that interact with RPL22L1a and RPL22L1b. First, each isoform was expressed in E. coli and immobilized on magnetic beads. The beads were incubated with GBM cell lysates and proteins bound to the beads were identified using LC-MS/MS.

2023-10-24 | PXD035849 | Pride

RNAseq transcriptomic profile of glioblastoma stem-like cells derived from U87MG cell line treated with a selective A3 adenosine receptor antagonist (MRS1220) under hypoxia

Project description:Glioblastoma Multiforme (GBM) is the primary brain tumor with the highest incident and mortality rates worldwide. This is because therapies are not effective, mainly due to tumor recurrence after surgical resection and chemotherapeutic treatment. Recurrence is mainly produced by a tumoral cell sub-population called Glioblastoma Stem-like Cells (GSCs), which are primarily responsible for chemo-resistance and tumor infiltration. We previously showed that in this sub-population, adenosine regulates chemo-resistance through its A3AR. The importance of this study lies in the confirmation that the adenosine/A3AR axis is a plausible therapeutic target to attack different features of GBM, including chemo-resistance and cell migration/invasion of GSCs.

2019-05-06 | GSE100146 | GEO

ZNF117 target ChIP-seq

Project description:Glioblastoma (GBM) is a deadly disease without effective treatment. Because glioblastoma stem cells (GSCs) contribute to tumor resistance and recurrence, improved treatment of GBM can be achieved by eliminating GSCs through inducing their differentiation. Prior efforts have been focused on studying GSC differentiation towards the astroglial lineage.

2022-02-08 | GSE196067 | GEO

Quiescent glioblastoma cells shift to an epithelial-mesenchymal transition-like gene program

Project description:Quiescent stem cells of glioblastoma (GBM), a malignant primary brain tumor, are potential sources for recurrence after therapy. However, the gene expression program underlying the physiology of GBM stem cells remains unclear. We have isolated quiescent GBM cells by engineering them with a knock-in H2B-GFP proliferation reporter and expanding them in a 3D tumor organoid model that mimics tumor heterogeneity. H2B-GFP label retaining quiescent cells were subjected to stem cell assays and RNA-Seq gene expression analysis. While quiescent GBM cells were similar in clonal culture assays to their proliferative counterparts, they displayed higher therapy resistance. Interestingly, quiescent GBM cells upregulated epithelial-mesenchymal transition (EMT) genes and genes of extracellular matrix components. Our findings connect quiescent GBM cells with an EMT-like shift, possibly explaining how GBM stem cells achieve high therapy resistance and invasiveness, and suggest new targets to abrogate GBM.

2019-04-22 | GSE114574 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data