Abstract 12: Metastatic neuroblastoma cancer stem cells display a mixed phenotype of tumor and niche origin required for survival
Bibliographic record
Abstract
Abstract Neuroblastoma (NB) is a pediatric tumor of neural crest origin, and is the most common cancer of infancy. 50% of patients have metastases at diagnosis, of which 85% will die after multiple relapses from metastatic disease. We identified tumor-initiating cells (TICs) from bone marrow (BM) metastases of high-risk patients that are propagated as spheres and that have many properties of cancer stem cells, and form NB in mice with as few as 1 cell. To understand patient relapse and disease progression, we compared NB-TICs from BM with those from tumor and brain metastases and SKPs, a normal pediatric stem cell counterpart, by cDNA microarray, flow cytometry, and whole genome shotgun sequencing transcriptome analysis. BM-derived NB-TICs expressed primitive neural crest and neuronal markers as well as hematopoietic markers from primitive, myeloid, and B-cell lineages and contained VDJ gene rearrangements, which are normally associated with B-cell leukemias. Hematopoietic genes were not expressed or expressed at very low levels in tumor-derived sphere lines and a line from an NB brain metastasis, however brain metastasis-derived TICs expressed CD133, while BM-derived NB-TICs did not. Furthermore, we found that shRNA to CD74, which is upregulated in B-cell lymphoma and multiple myeloma and is a therapeutic target for those cancers, induced the rapid death of NB-TICs but not normal SKPs. Interestingly cells co-staining for the hematopoietic markers CD45 or CD74 and the neural neural progenitor marker nestin were found in BM smears of patients with relapsed NB in the bone marrow. We suggest that metastatic TICs from some tumors adopt resident niche-specific gene expression signatures, which may aid diagnosis and the development of novel treatments. We hypothesize that drugs used for leukemia may be efficacious therapeutics for metastatic NB, and are currently testing this hypothesis in mouse models. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 12.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".