Abstract PR15: Acting at a distance: Medulloblastoma-secreted ligands disrupt normal neural stem cell function
Bibliographic record
Abstract
Abstract Long-term cognitive impairments are common in pediatric brain cancer survivors. While these impairments are thought to arise following radiation treatment, recent reports suggest a link to tumor-specific mechanisms. We therefore hypothesized that pediatric brain tumors, more specifically medulloblastoma (MB), can directly affect neural stem and precursor cell function in the forebrain stem cell niche—the subventricular zone (V-SVZ) —by secreting bioactive factors. Mice harboring subcutaneous flank MB tumors had fewer proliferating neural precursor cells in the V-SVZ than controls as well as decreased olfactory bulb neurogenesis and white matter oligodendrogenesis. To assess the effects of the MB secretome in the brain, concentrated conditioned media from MB cell lines (MB-CM) was injected intracerebroventricular (ICV) into mouse pups. ICV injection of MB-CM decreased neural precursor cell proliferation as well as decreased numbers of V-SVZ neurospheres in culture. MB-CM from multiple cell lines decreased V-SVZ neurosphere number and promoted astrocyte differentiation in culture. To identify the ligands contributing to the phenotype, an interaction model was developed extracting ligands from MB microarray data, networking them to receptors on NSCs. Of the predicted ligands, IL6-family cytokine expression and secretion was validated in MB cells. When added in culture, recombinant IL6, IL11, and CT1 decreased neurosphere number and ICV injection of IL11 into mouse pups decreased V-SVZ neural precursor cell proliferation. Overall, this work demonstrates that medulloblastoma secretes bioactive compounds that perturb neural stem cell function and the circuity involved in normal cognitive function. This abstract is also being presented as Poster B64. Citation Format: Alexander Gont, Jaclin V. Simonetta, Jenna Park, Alice R. Shan, Michael J. Borrett, Michael D. Taylor, Freda D. Miller, David R. Kaplan. Acting at a distance: Medulloblastoma-secreted ligands disrupt normal neural stem cell function [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr PR15.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".