|
| Status |
Public on Oct 30, 2024 |
| Title |
Endothelial-secreted Endocan protein acts as a PDGFR alpha ligand and regulates vascularity, radioresistance, and regional phenotype in glioblastoma [1] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
One of the hallmarks of glioblastoma (GBM) is extensive neovascularization. In addition to supplying blood and nutrients, vascular endothelial (VE) cells provide trophic support to GBM cells via paracrine signaling, the precise mechanisms of which are being unraveled. Here, using patient-derived GBM and VE cells as well as orthotopic GBM mouse models, we report that Endocan (ESM1), an endothelial-secreted proteoglycan, confers enhanced proliferative, migratory, and angiogenic properties to GBM cells and regulates their spatial identity. Mechanistically, Endocan exerts at least part of its functions via direct binding and activation of the PDGFRA receptor. Subsequent downstream signaling enhances chromatin accessibility of the Myc promoter and upregulates Myc expression inducing highly stable phenotypic changes in GBM cells. Furthermore, Endocan confers a radioprotection phenotype in GBM cells, both in vitro and in vivo. Inhibition of Endocan-PDGFRA signaling with ponatinib increases survival in the Esm1 wild-type but not in the Esm1 knock-out mouse GBM model. Our findings identify Endocan and its downstream signaling axis as a potential target to subdue the recurrence of GBM and further highlight the importance of vascular to tumor cell signaling for GBM biology.
|
| |
|
| Overall design |
There are three groups: Control only (n=4), 1079 cells treated with 10ng/ml Endodcan (n=4) or 10ng/ml of PDGFBB for 72 hours. We then performed RNAseq of these samples and performed gene expression analyses.
|
| |
|
| Contributor(s) |
Bastola S, Pavlyukov M, Gao F, Kawaguchi R, Kornbmum H |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Sep 12, 2024 |
| Last update date |
Oct 30, 2024 |
| Contact name |
Riki Kawaguchi |
| Organization name |
University of California, Los Angeles
|
| Department |
Department of Psychiatry and Neurology Department of Psychiatry
|
| Lab |
AMRF Functional Genomics Common Research Resource
|
| Street address |
760 Westwood Plaza, Room 37-420
|
| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095-1759 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (12)
|
|
| This SubSeries is part of SuperSeries: |
| GSE277015 |
Endothelial-secreted Endocan protein acts as a PDGFR alpha ligand and regulates vascularity, radioresistance, and regional phenotype in glioblastoma |
|
| Relations |
| BioProject |
PRJNA1160226 |
Less...
More...