MT1-MMP is the critical determinant of matrix degradation and invasion by ovarian cancer cells
Bibliographic record
Abstract
Membrane-type 1 matrix metalloproteinase (MT1-MMP), a transmembrane metalloprotease that plays an important role in the invasion of many solid tumour types, promotes pericellular matrix degradation and may also stimulate tumour cell motility. As both these processes are key contributors to intraperitoneal ovarian tumour metastasis, we examined six ovarian cancer cell lines to determine whether MT1 is a critical mediator of invasive behaviour for this tumour type. Our results indicated that only those cell lines that expressed MT1 were capable of penetrating a type I collagen barrier, with the capacity for both matrix degradation and invasion reflecting endogenous MT1 expression level. Ectopic MT1 expression endowed an invasive phenotype upon cell lines lacking MT1 that were previously non-invasive, indicating the crucial role of this protease. Conversely, invasion was abolished by tissue inhibitor of metalloproteinase-2 (TIMP-2), a potent inhibitor of MT1, yet was minimally affected when other (secreted) MMPs were inhibited using TIMP-1 and the gelatinase inhibitor SB-3CT. Whereas collagen I degradation was strikingly accelerated by ectopic MT1 expression, cell motility remained unchanged. We conclude that MT1 is necessary for collagen I invasion by ovarian cancer cells, and that its requisite activity is the promotion of matrix degradation, with no impact on cell motility.
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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 | 0.000 | 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 | 0.000 |
| 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".