A121 DEVELOPMENT OF COLON CANCER MODELS TO STUDY THE INTERACTION BETWEEN CANCER STEM CELLS AND THE MICROENVIRONMENT
Bibliographic record
Abstract
Abstract Background Colon cancer is the 2nd deadliest cancer worldwide. The main treatment combines surgery with 5-fluorouracil (5-FU) chemotherapy. However, the number of relapses remains frequent due to a loss of sensitivity to treatment, known as chemoresistance. Over the last decades, studies have highlighted the importance of two tumoral components: cancer stem cells (CSC) and the microenvironment. CSC are tumor cells characterized by their enhanced capacity for self-renewal, potency and resistance to anti-cancer treatments. The microenvironment, for its part, comprises all components surrounding the tumor cells including cancer-associated fibroblasts (CAF). While their respective importance in resistance has been studied, it is important to better understand their interactions during resistance and how this could affect their respective functions. Aims Identify the specific changes occurring in CSC and the impact of their interaction with CAF during the induction of 5-FU resistance in colon cancer. Methods To achieve this goal, we established a model of colon cancer organoids resistant to 5-FU. Results First, we validated that the parental organoids maintained their expected cellular heterogeneity. Indeed, the presence of proliferative cells (Ki67+) and CSC (ALDH1+) was confirmed by immunofluorescence. We also confirmed that they are sensitive to 5-FU by assessing cell survival using a WST1 assay. With a baseline IC50 of 7µM, we concluded that they can be used to generate a 5-FU resistant line. To induce 5-FU resistance, we performed cyclic treatments to mimic clinical reality using a 5-FU dose 4-5 times greater than the baseline IC50. Resistance is currently being validated by WST1 assay to compare IC50. Second, our initial findings indicate that the conditioned media of CAF cultures reduce the sensitivity of parental organoids to 5-FU, highlighting the necessity for further exploring the interaction between these two tumor components. Conclusions In summary, our preliminary results suggest that the interaction between tumor cells and CAF influences the sensitivity to chemotherapy. We are currently investigating the interaction between CAF and CSC with secretome and surfaceome analysis. Additionally, we are investigating the phenotypic and transcriptomic changes occurring specifically in CSC isolated from resistant organoids. Ultimately, the aim of this project is to enhance our understanding of the changes required for resistance, paving the way for new targeted therapies. Funding Agencies Canada foundation for innovation, 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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".