Abstract 4093: Cadherin “switch” and ovarian cancer: Studies using in vitro models and patient samples
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Abstract Ovarian cancer (OC) is the 5th leading cause of cancer deaths in women worldwide due to late symptoms and its diagnosis at advanced stages. Epithelial to mesenchymal transition (EMT) is an important step in cancer invasion/metastasis and downregulation of Epithelial cadherin (Ecad) is a critical feature of this process. Ecad expression was evaluated in 100 OC tissue sections, finding a decreased Ecad signal along tumor stage, with highest expression in stage I/II (no invasive) and lowest in stage IV (invasive) tumors. These results are in agreement with previous reports showing reduced Ecad expression in correlation with poor prognosis in OC patients. In some cases, Ecad downregulation is accompanied by increased Neural cadherin (Ncad) expression and acquisition of migratory/mesenchymal features. Although this cadherin “switch” has been reported in OC, current data is inconclusive. Expression of Ecad, Ncad and other EMT markers was studied in 4 OC cell lines and according to their levels they were classified as epithelial (OV90), intermediate epithelial (OAW42), intermediate mesenchymal (SKOV3) and mesenchymal (TOV112) cells. The mechanisms underlying regulation of Ecad levels were evaluated by assessing expression of its transcriptional repressors Twist, Snail, Slug, Zeb1. Migration properties were also studied, being significantly higher in TOV112 and SKOV3 cells. It has been proposed that OC cells shed from the primary tumor aggregate as spheroids in the ascites, maintain cellular contacts and survive in suspension. To mimic ovarian tumor cell dissemination through the ascites and to evaluate the role of the cadherin “switch” in this process, cell lines were grown under anchorage-independent conditions. The aggregates number/area was analyzed, being the SKOV3 spheroids the most compacted. When Ecad, Ncad and EMT markers expression was determined similar findings were obtained when spheroids were compared to monolayers, suggesting an intrinsic cell gene expression pattern rather than a response to a cell culture growth condition. The OC spheroids survival was assessed by estimating cell death, finding a positive correlation between high Ncad levels and cell aggregates with low% cell death. Spheroid adhesion/dissemination in extracellular matrices and 3D-spheroid matrigel assays were done to assess invasion at a secondary site. Spheroids from cells with mesenchymal/intermediate mesenchymal phenotypes adhered to extracellular matrices and invaded more than cells with intermediate epithelial/epithelial phenotypes. Finally, Ecad/Ncad expression studies done on primary cultures derived from tumor and ascitic cells from patients with OC revealed a diminished Ecad and a higher Ncad expression in ascitic cells compared to primary tumor cells. Altogether, the data here presented reveals an association between OC cell aggressiveness and a mesenchymal-like molecular profile; and it depends on the expression of Ecad and Ncad markers. Citation Format: Marina Rosso, Blanca Majem, Laura Devis, Lara Lapyckyj, Marta Llauradó, Lucía Lanau, María Florencia Abascal, María Laura Matos, María José Besso, Josep Castellví, Jose Luís Sanchez-Iglesias, Asunción Pérez-Benavente, Antonio Gil-Moreno, Jaume Reventós, Marina Rigau, Mónica Vazquez-Levin. Cadherin “switch” and ovarian cancer: Studies using in vitro models and patient samples. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4093. doi:10.1158/1538-7445.AM2015-4093
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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 | 0.000 | 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 it