Beta(3) integrin expression increases breast carcinoma cell responsiveness to the malignancy-enhancing effects of osteopontin.
Bibliographic record
Abstract
Osteopontin (OPN) is a secreted phosphoprotein that has been associated with malignancy of breast and other cancers. OPN binds to several cell surface integrins including alpha(v)beta(3), alpha(v)beta(5), and alpha(v)beta(1). Although the relative contribution of these integrins to breast cancer cell malignancy is uncertain, correlative studies suggest that alpha(v)beta(3) may be particularly associated with increased tumor aggressiveness. Previously, we reported that tumorigenic, nonmetastatic 21NT mammary carcinoma cells respond to OPN through alpha(v)beta(5) and alpha(v)beta(1) but not alpha(v)beta(3). Here, we determined that 21NT cells lack beta(3) expression, and we asked whether expression of alpha(v)beta(3) could enhance the ability of breast cancer cells to respond to the malignancy-promoting effects of OPN both in vitro and in vivo. 21NT cells stably transfected with beta(3) showed significantly increased adhesion, migration, and invasion to OPN in vitro compared with vector control. To determine if beta(3) could also enhance the response of breast epithelial cells to OPN in vivo, cells stably transfected with both beta(3) and OPN (NT/Obeta(3)) were injected into the mammary fat pad of female nude mice and primary tumor growth was assessed relative to controls. Mice injected with NT/Obeta(3) cells demonstrated a significantly increased primary tumor take (75% of mice) compared with controls (0-12.5% of mice) as well as a decreased tumor doubling time and a decreased tumor latency period. These results suggest that increased expression of the alpha(v)beta(3) integrin during breast cancer progression can make tumor cells more responsive to malignancy-promoting ligands such as OPN and result in increased tumor cell aggressiveness.
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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 | 0.001 |
| 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".