RANKL/OPG expression ratio in prostate cancer cell lines with varying bone metastatic potential
Bibliographic record
Abstract
4087 Metastasis to bone can lead to extreme pain, deregulation of calcium, fractures, immobility and ultimately death. Bone metastatic lesions from prostate cancer are recurrent in 10-20% of patients who have undergone surgery to remove tumors. Current treatments for bone metastases are only palliative and include bisphosphonates and radiotherapy, but no effective curative treatment exists. Recently, the cytokine triad involved in regulating bone remodeling, osteoprotegerin (OPG), Receptor Activator of NF-κB ligand (RANKL) and Receptor Activator of NF-κB (RANK), has been examined as a possible therapeutic target in preventing bone metastasis from primary tumors. RANKL acts as an activator of osteoclastogenesis and osteoclast survival by binding to its cognate receptor RANK. This interaction has been identified as a causal factor for the osteolytic phenotype seen in various bone diseases. OPG is a decoy receptor for the interaction of RANK and RANKL, and inhibits bone resorption. Recently, it has been suggested that the pattern of lesions identified in prostate cancer bone metastasis varies depending on the tumor microenvironment and is directly dependent on the RANKL/OPG ratio. Although evidence does imply the role of the cytokine triad OPG/RANKL/RANK in prostate cancer bone metastases, little is known about the changes that are elicited at the primary tumor site and the bone metastatic site. Here we investigated the changes in the RANKL/OPG ratio in prostate cancer cell lines with varying bone metastatic potential. We used the following human prostate cancer cell lines: CL-1, LNCaP, PC-3, DU-145, MDA-PCa2b, and 22Rv1. Western blotting analysis, ELISA, semi-quantitative PCR and real-time PCR measurements were used to quantify the ratio of these two cytokines between the cell lines. OPG gene expression was found to be 2- and 3-fold higher in CL-1 cells compared to PC-3 and LNCaP cells, respectively, while RANKL gene expression was 3- and 2-fold higher in PC-3 and LNCaP cells, respectively, compared to CL-1 cells. These results suggest that the RANKL/OPG ratio was lower in CL-1 cells and higher in PC-3 and LNCaP cells. Hence, the diversity of the prostate cancer phenotype in vitro suggests a potential role for the OPG/RANKL/RANK triad in mediating the type of bone metastatic lesions (osteoblastic vs. osteolytic). Financial support is provided by the Prostate Cancer Research Foundation of Canada
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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 | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 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".