Effects of soluble factors released by oral squamos cell carcinoma on osteoclasts
Bibliographic record
Abstract
Objective: Bone invasion represent significant problem in managing head and neck cancers, however the mechanisms of interactions between oral squamous cell carcinoma (OSCC) and bone cells are poorly understood. We hypothesized that tumor cells can directly stimulate osteoclastogenesis. Methods: OSCC cell lines, bone-invasive BHY and metastatic but not bone-invasive HN were cultured and conditioned medium (CM) was collected. Osteoclast formation from RAW 264.7 mouse monocytic cell-line was assessed. Results: When RAW 264.7 were primed with receptor activator of nuclear factor κB ligand (RANKL) and then treated with BHY-CM, marked 2-6 fold induction of osteoclastogenesis was observed. In contrast, HN-CM did not significantly affect osteoclastogenesis. In addition, BHY-CM, but not HN-CM promoted survival of mature osteoclasts. Using pharmacological inhibitors, we found that Protein kinase C (PKC)/Extracellular signal-regulated kinase (ERK)1/2/Mitogen activated protein kinase (MAPK) p38 as well as Phosphatidyl-inositol 3-kinases (PI3K)/Serine/threonine protein kinase Akt/Mammalian target of rapamycin (mTOR) pathways mediate BHY-CM induced osteoclastogenesis. Conclusion: OSCC-cells produce soluble factors that stimulate osteoclastogenesis from RANKL-primed precursors. Tumor-derived factors act by stimulating ERK1/2 and p38 MAPK pathways in osteoclast precursors.
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How this classification was reachedexpand
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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.002 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.004 |
| 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; both teacher heads agree on what is shown here.
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".