Analysis of epithelial ovarian cancer morphology, adhesion and migration in response to bone morphogenetic protein 4
Bibliographic record
Abstract
3770 Introduction Bone morphogenetic proteins (BMPs) are members of the transforming growth factor beta (TGFβ) superfamily of secreted ligands. We have identified a functional BMP signaling pathway in human ovarian surface epithelial (OSE) and epithelial ovarian cancer (EOC) cells. Most ovarian cancers arise from the OSE, which forms a monolayer covering the ovarian surface and rests on a basement membrane composed of extracellular matrix (ECM) proteins such as collagen IV and laminin. OSE and EOC cells express integrin receptors and focal adhesion proteins that facilitate adhesion to the ECM. These molecules likely play a role in repair mechanisms following the rupture of the OSE after ovulation and may contribute to EOC metastasis. We have shown that the treatment of EOC cells with BMP4 results in altered cell morphology characterized by increased cell spreading. We hypothesize that BMP4 signaling induces changes in cell morphology, adhesion and migration by altering the cytoskeleton, integrin receptors and ECM. Methods Primary human EOC cells were left untreated or grown in the presence of 10 ng/mL BMP4 for 7 days. Cytoskeletal changes were visualized through staining of filamentous actin (F-actin), while integrin receptor and focal adhesion protein localization was observed by immunofluorescence. Quantitative PCR was used to assess mRNA levels of integrin receptors, focal adhesion proteins and ECM proteins. Motility of EOC cells in response to BMP4 was evaluated using an in vitro wounding assay while cell adhesion was observed using a tritiated amino acid incorporation assay. Results Consistent with cell spreading, increased stress fiber formation occurred in response to BMP4 treatment. In addition, localization of vinculin to an apparent greater number of focal contacts along with colocalization to actin stress fibers was observed. Changes in the staining pattern of integrins α3, α5, αV and β1 were seen with BMP4 treatment. Quantitative PCR analysis showed modest increases in integrin receptor and focal adhesion protein mRNA after 7 days of treatment, while marked increases in collagen I, collagen IV and filamin mRNA levels were seen as early as 24hrs following BMP4 treatment. EOC cells demonstrated increased motility in the presence of BMP4, while showing decreased cell adhesion. Conclusions Taken together, this data shows that BMP4 can induce changes in molecules involved in cell morphology, adhesion and motility, translating into changes in cellular behavior. Future work will examine these behaviors with BMP4 treated EOC cells in response to culture on various ECM substrates, and comparison with normal OSE samples. These experiments will enhance our understanding of how BMP4 signaling may contribute to metastasis.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".