Cyclooxygenase-2 Confers Growth Advantage to Syngeneic Pancreatic Cancer Cells
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Bibliographic record
Abstract
Objectives: Targeting the cyclooxygenase-2 (COX-2)/prostanoid pathway is considered an intriguing approach for therapy and prevention of several cancers. However, the molecular mechanisms that underlie the protumorigenic properties of COX-2 in pancreatic cancer (PaCa) are still poorly understood. The purpose of the present study was to characterize the phenotype of COX-2 expressing syngeneic PaCa cells. Methods: Cyclooxygenase-2-negative MIA PaCa-2 cells were stably transduced with COX-2 or control viruses (MP2+COX-2 and MP2−COX-2). Prostaglandin E2 (PGE2) production was measured by liquid chromatography and tandem mass spectrometry. Anchorage-dependent and -independent cell growth was analyzed by cell count and 3-dimensional collagen cell culture system, respectively. Changes in apoptotic gene expression were measured by a polymerase chain reaction array. The growth of tumors in vivo was evaluated in a xenograft animal model. Results: Stable expression of COX-2 increased anchorage-dependent and -independent cell growth, which was accompanied by elevated PGE2 production. Several significant differences in apoptotic gene expression were detected between MP2+COX-2 and MP2−COX-2 cells. Furthermore, MP2+COX-2 cells grew faster than MP2−COX-2 cells in a xenograft animal model. Conclusions: Our results will provide the basis for more mechanistic studies on the role of COX-2 in PaCa and may help to develop novel therapeutic strategies aiming at the COX-2/prostanoid pathway. Abbreviations: COX-2 - cyclooxygenase-2, PGE2 - prostaglandin E2, PaCa - pancreatic cancer, LC-MS/MS - liquid chromatography and tandem mass spectrometry, AA - arachidonic acid, cPLA2 - cytoplasmic phospholipase A2, mPGES - microsomal prostaglandin E synthases, cPGES - cytoplasmic prostaglandin E synthases
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.001 | 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 it