Proteinase‐activated receptor (PAR)‐2 stimulates cyclooxygenase‐2 (COX‐2) expression in Caco‐2 colon cancer cells: role of matrix metalloproteinases (MMPs)
Bibliographic record
Abstract
Colon cancer is associated with elevated levels of trypsin, an activator of PAR 2 ; PAR 2 activation stimulates MMP‐9 release and COX‐2 expression, which are both involved in inflammation and cancer. We hypothesize that MMPs participate in PAR 2 ‐induced COX‐2 expression in Caco‐2 colon cancer cells. Cells were treated for 3hr with PAR 2 #‐activating peptide (fLI) with or without a pan‐MMP inhibitor. Concentrated, conditioned media from treated cells were used to treat separate cells. Other cells were treated directly with activated MMP‐9 or tissue inhibitor of metalloproteinase (TIMP)‐1, an endogenous MMP inhibitor with greater selectivity for MMP‐9. COX‐2 expression was assessed by western blot. Secreted MMPs were analyzed by zymography. The pan‐MMP inhibitor decreased fLI‐induced COX‐2 expression in Caco‐2 cells. Concentrated, conditioned media from fLI‐treated cells induced COX‐2 expression in separate cells. TIMP‐1 did not suppress PAR 2 ‐induced COX‐2 expression nor did direct treatment with MMP‐9 increase its expression. Caco‐2 cells secrete gelatinases and casein‐degrading MMPs. It is unclear yet whether PAR 2 activation alters the secreted MMP profile. In summary, PAR 2 activation stimulates COX‐2 expression via a MMP other than MMP‐9 in Caco‐2 cells. Understanding this pathway may help define molecules to target in the progression from inflammation to cancer. Funded by CAG/CIHR/Abbott.
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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 | 0.001 |
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".