SMPD3-mediated extracellular vesicle biogenesis inhibits oligodendroglioma growth
Bibliographic record
Abstract
Abstract Oligodendrogliomas are lower-grade, slow-growing gliomas that are ultimately fatal. Although driver mutations are known, the mechanisms underlying their signature slow growth rates are poorly understood. We found evidence for intra-tumoral interactions between neoplastic and non-neoplastic cells in oligodendroglioma tissues. To further study these cell interactions, we used two patient-derived oligodendroglioma cell lines of lower and higher aggressivity. Both oligodendroglioma cell lines released extracellular vesicles that had cytotoxic effects on non-neoplastic and neoplastic cells, but each had distinct vesicular proteomes. Consistent with extracellular vesicles mediating growth inhibitory effects in oligodendrogliomas, higher expression levels of several extracellular vesicle biogenesis genes (SMPD3, TSG101, STAM1) correlates with longer survival in oligodendroglioma patients. Furthermore, SMPD3 overexpression slows oligodendroglioma cell growth in culture. Conversely, SMPD3 knockdown enhances oligodendroglioma proliferation in vitro, in murine xenografts, and in human cerebral organoid co-cultures. Oligodendroglioma-derived extracellular vesicles thus mediate tumor cell microenvironmental interactions that contribute to low aggressivity.
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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 | 0.011 | 0.011 |
| Meta-epidemiology (narrow) | 0.001 | 0.002 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.004 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.005 | 0.012 |
| Research integrity | 0.002 | 0.006 |
| Insufficient payload (model declined to judge) | 0.001 | 0.002 |
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; both teacher heads agree on what is shown here.
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".