The role of the tumor microenvironment: The matricellular protein CCN2/CTGF is essential for melanoma metastasis
Bibliographic record
Abstract
M the second most common invasive cancer in young adults, is highly metastatic: ~5% of patients diagnosed with metastatic melanoma survive for 5 years after diagnosis. 40-60% of all cutaneous melanoma patients possess mutations in BRAF; in these patients, tumors shrink in response to the BRAF inhibitors. However, patients develop resistance to these drugs, necessitating the development of alternative therapeutic targets. The matricellular protein connective tissue growth factor (CCN2) is overexpressed in melanoma; however, how CCN2 contributes to melanoma progression is unclear. Herein, we use melanoma cell lines and mice in which CCN2 is deleted in the tumor stroma to demonstrate that loss of CCN2 in the tumor microenvironment impedes melanoma invasion. Specifically, loss of CCN2 in melanoma cells diminished their ability to invade through collagen in vitro and loss of fibroblast derived CCN2 decreased metastases of melanoma cells from the skin to the lungs in vivo. CCN2 deficient B16(F10) cells showed reduced expression of periostin; addition of recombinant periostin rescued the in vitro invasion defect of these cells. Analysis of CCN2 deficient mice confirmed loss of periostin expression in the absence of CCN2. CCN2 and periostin mRNA levels are positively correlated with each other and with the stromal composition of human melanoma lesions but not BRAF mutations. These results are consistent with the idea that metastatic ability results from CCN2 mediated interactions between tumor cells and the stroma. CCN2 promotes invasion and metastasis via periostin and should be further evaluated as a possible therapeutic target for BRAF inhibitor-resistant melanoma.
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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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| 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".