9 D-SERINE FACILITATES AGGRESSIVE MIGRATION AND STEMNESS OF RECURRENT GLIOBLASTOMA CELLS BY INTERACTING WITH HOST ENDOTHELIAL CELLS
Bibliographic record
Abstract
Abstract Sponsored by BC Cancer Foundation Introduction: Glioblastoma (GBM) cells infiltrate deep brain structures by exploiting perivascular pathways, utilizing stem-like properties and malignant traits to access nutrient-rich environments that support tumor expansion. Our findings suggest that N-methyl-D-aspartate receptors (NMDARs) in brain endothelial cells play a key role in transducing signals initiated by parenchymal cells, facilitating recurrent GBM progression. Hypothesis: D-serine enhances GBM migration and stemness by interacting with host endothelial cells, thereby promoting recurrent tumor aggressiveness. Methods: Patient-derived recurrent GBM cells and human cerebral microvascular endothelial cells (hCMECs/D3) were co-cultured in a transwell system to assess the role of endogenous D-serine in GBM migration and stemness. Pharmacological inhibitors, CRISPR/Cas9-mediated gene silencing, and enzymatic modulation of D-serine metabolism were employed to determine the contribution of GBM-derived D-serine and endothelial NMDARs to these processes. Further, in vivo xenograft experiments employed gene silencing or pharmacological inhibitors of Serine Racemase (SRR) to test the effects of recurrent tumorigenesis. Results: Endothelial cells significantly potentiated GBM migration and stemness in co-culture. D-serine release from GBM cells was confirmed using D-amino acid oxidase, SRR inhibition with phenazine methosulfate (PMS), and CRISPR-mediated SRR silencing, significantly reducing migration and stemness markers. Pharmacological NMDAR antagonism and endothelial GluN1 silencing further mitigated these effects. In vivo, SRR silencing, or inhibition, reduced tumor burden at 4 weeks post-injection and extended survival in GBM-bearing mice. Conclusion: Our findings demonstrate that brain endothelial cells enhance GBM malignancy through D-serine- mediated activation of endothelial NMDARs. This pathway supports GBM migration and stemness, presenting a novel therapeutic target for recurrent GBM treatment.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".