A10 PROLINE METABOLISM AFFECTS CANCER STEM CELLS IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Bibliographic record
Abstract
Abstract Background Esophageal squamous cell carcinoma (ESCC) is highly deadly with a 5-year survival rate of only 16%, partly due to treatment resistance. Resistance is associated, among others, with the presence of cancer stem cells (CSC). Previous work in the laboratory has shown that prolonged exposure to anticancer treatments such as radiation and/or 5-FU leads to increased number of CSCs. Interestingly, disruption of amino acid metabolism, especially decreased proline levels, has been observed in treated cells. Proline is a non-essential amino acid that can either be uptake from the environment or synthesized from glutamate or ornithine. However, its role in cancer cells remains poorly understood and controversial. Aims Therefore, my project aims at determining the role of proline metabolism in CSC abundance and tumoral properties in ESCC. Methods Using ESCC cell lines, TE11 and TE15, we stimulated proline metabolism by adding proline to the media or inhibited its catabolism using L-THFA. L-THFA forces proline accumulation in the cell. We then conducted flow cytometry to quantify CSC proportion, proliferation assay, spheroid formation assay and spheroids included in collagen for migration and invasion assay. Results First, the stimulation of proline metabolism decreased the proportion of CSCs in flow cytometry. These results align with our initial observations, where CSC-enriched cells exhibited reduced proline levels. Second, the inhibition of proline catabolism by L-THFA had the opposite effect, namely an increase in the proportion of CSC. Interestingly, these changes in the proportion of CSCs induced by proline or L-THFA translated into changes in clonogenic potential, a capacity typically associated with stem cells. Indeed, limiting dilution spheroids formation assays showed that proline decreased while L-THFA increased the number of formed spheroids. Since spheroids formation is linked to the presence of CSC, this provides new evidence of the impact of proline metabolism on CSC characteristics. Finally, L-THFA treatments drastically increased migratory and invasive abilities in 3D spheroid models compared to untreated or proline-treated conditions. Conclusions In conclusion, our results suggest that proline metabolism is implicated in the enrichment of cancer stem cells as well as in their functions. Funding Agencies CAG, CIHRinnovation.ca ; Centre de recherche CHUS ; FMSS ; Canada Research Chairs
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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) | 0.002 | 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".