Abstract P6-07-01: CCN3 Impairs Osteoblasts and Stimulates Osteoclast Differentiation To Favor Breast Cancer Metastasis to Bone
Bibliographic record
Abstract
Abstract Background: The mechanisms underlying the osteotropism of breast cancer are not fully understood. Breast cancer cell lines that aggressively metastasize to bone appear to have increased expression of CCN3 (Nov) compared to those that weakly metastasize to bone. This study aimed to functionally implicate CCN3 in the process of breast cancer metastasis to bone. Methods: Primary cultures of mouse bone marrow cells were used to assess the effect of recombinant CCN3 protein on RANKL, OPG and on osteoblasts and osteoclasts. To extend data obtained from cell and animal-based models, we have examined CCN3 expression a panel of human breast cancer bone metastases. Results: CCN3 protein impaired osteoblast differentiation in a dose dependant manner, resulting in an increase in the RANKL/OPG ratio that indirectly favors osteoclast formation. CCN3 also directly induced osteoclast differentiation of RANKL-primer RAW 264.7 monocytes. CCN3 enhanced osteoclast differentiation through its ability to induce calcium mobilization and the subsequent nuclear translocation of NFATc1, a transcription factor essential for osteoclast differentiation. Immunohistochemical staining indicated that CCN3 is readily detectable, both in the breast tumor/stroma and in the majority of breast cancer bone metastasis samples. Conclusion: Our data support a clinically relevant and important role for CCN3 in modulating the differentiation capacity of bone resident cells to support osteoclast formation and the formation of osteolytic bone metastases. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-07-01.
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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 | 0.000 |
| 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 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 teacher head, 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".