CD40 activation in epithelial ovarian carcinoma cells modulates growth, apoptosis, and cytokine secretion
Bibliographic record
Abstract
BACKGROUND/AIMS: CD40, a member of the tumour necrosis factor (TNF) receptor family, is expressed on a variety of haematopoietic cells and is crucial in orchestrating both humoral and cellular immune responses. CD40 is also expressed on some carcinoma cells, where its function remains largely unknown. This study investigated the effects of CD40 ligation on ovarian carcinoma cell growth and apoptosis and on cytokine production, in addition to the role of the NF-kappa B and JNK signalling pathways. METHODS: CD40 expression was measured in epithelial ovarian carcinoma (EOC) biopsies by immunohistochemistry and in EOC cell lines by flow cytometry. To examine the effects of CD40 ligation on cell growth recombinant soluble CD40 ligand was used to stimulate EOC cell lines and growth was measured by MMT assays. Cytokine production was measured by enzyme linked immunosorbent assays interleukin 8 (IL-8) gene transcription was estimated by means of reverse transcription polymerase chain reaction. The integrity of the CD40 signalling pathway in those cell lines that did not produce cytokines in response to CD40 ligation was assessed by the detection of the transcription factor NF-kappa B by an electrophoretic mobility shift assay. To investigate the defect in the NF-kappa B pathway the phosphorylation status of I kappa B alpha was determined by an antibody specific to phosphorylated I kappa B alpha and dissociation of the I kappa B alpha-p65 complex was assessed by co-immunoprecipitation. RESULTS: CD40 is expressed in primary ovarian carcinoma biopsies and EOC cell lines. CD40 ligation resulted in growth inhibition in most of these carcinoma cell lines and was also found to promote apoptosis, with this last effect only being evident in early passage EOC cells. CD40 ligation also induced significant IL-6 and IL-8 production in most of the EOC cell lines examined and it was confirmed for IL-8 that this effect was regulated at the transcriptional level. NF-kappa B activation in response to CD40 ligation was found in three of the EOC cell lines and specific defects in the CD40 induced NF-kappa B pathway were identified in two cell lines. However, CD40 engagement induced JNK activation in all the EOC cell lines. CONCLUSIONS: These data suggest that the CD40 pathway is functional in ovarian carcinoma cells and highlight the need for further studies to provide insight into the role of CD40 in the carcinogenic process and the possible exploitation of this pathway for novel therapeutic approaches.
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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".