Expression of matricellular protein CCN1 in the tumor stroma is required for melanoma metastasis
Bibliographic record
Abstract
Metastatic melanoma has an extremely poor prognosis. BRAF inhibitors are used to treat a subset of patients but eventually patients acquire resistance to this therapy. An increasing body of evidence suggests that an activated tumor stroma is responsible for the acquisition of resistance to chemotherapy. Herein, we find that he secreted matricellular protein cyr61(CCN1) is overexpressed in human melanoma in a fashion that correlates negatively with clinical outcome, positively with the extent of tumor stroma development and not at all with BRAF mutational status. We have used a fibroblast‐specific type I collagen promoter‐driven cre recombinase that is tamoxifen dependent to generate C57BL6 mice deleted or not for CCN1 in fibroblasts. CCN1‐deficicent mice display progressive reduction in skin thickness. When injected subcutaneously, B16(F10) cells show reduced metastasis to the lung. Tumor growth is unaffected. This phenotype is linked with reduction in expression of collagen‐modifying enzymes LOX, P4H and PLOD2 as well as a decrease in insoluble collagen protein expression as visualized by a hydroxyproline assay and by trichrome staining. Type I collagen mRNA expression is unaffected.. Thus, CCN1 is required for proper induction of a tumor stroma and hence for metastasis and thus should be further evaluated as a possible therapeutic target for BRAF inhibitor‐resistant melanoma. Support or Funding Information CIHR, Canadian Cancer Society
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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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".