Abstract 5204: Nodal regulates invasive phenotypes in extravillous and choriocarcinoma trophoblast cells
Bibliographic record
Abstract
Abstract Nodal, an embryonic morphogen and a member of the transforming growth factor-beta (TGF-ß) superfamily, is highly expressed in embryonic development and some cancers such as breast cancer and melanoma. It has been noticed that altered Nodal expression leads to changes in cellular invasiveness both during embryogenesis and cancer metastasis. However, the roles of Nodal in trophoblast invasion and tumor progression remain unclear. The present study characterizes and examines the effects of Nodal on cell migration, invasion and proliferation by using a highly invasive first trimester trophoblast cell line, HTR-8/svneo, and three Chrioncarcinoma cell lines as in vitro models. By knocking down Nodal expression with small hairpin RNA (shRNA) plasmid DNA and morpholino oligomers, stable and transient Nodal knockdown clones were created. RT-PCR and Western Blots were performed and analyzed to verify Nodal knockdown in comparison to the Non-transfected (control) cells. To further confirm successful Nodal knockdown, downstream Nodal signalling (phospho-Smad2) was tested and analyzed by Western Blot. Nodal knockdown cells were then subjected to: (1) growth curves to evaluate the effect of nodal level on cell growth capacity and viability; (2) transwell migration assays to assess the effect of Nodal on cell movement and mobility; (3) transwell invasion assays to investigate the effect of nodal on cell invasive potential. The data show that knockdown of Nodal results in a decrease in cell migration and invasion, but does not significantly alter proliferation in vitro. Furthermore, the addition of human recombinant Nodal results in a restoration of cell migration and invasion. In order to further confirm the involvement of Nodal in trophoblast invasion, and to correlate Nodal levels to trophoblast cell phenotype, we then quantified the amount of Nodal in three chrioncarcinoma cell lines (Jar, Jeg-3 and Bewo) with Western Blot, and checked their migratory and invasive potential by Transwell migration and invasion assays. The data show strong positive correlation between Nodal protein level and the cell migration and invasion capacity. Our data indicate that Nodal does play a significant role in trophoblast cell migration and invasion, the two major processes of tumor progression. By studying the first trimester invasive trophoblast cell line, a greater understanding about the role of Nodal shared by trophoblast invasion and tumor metastasis may be gained. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5204.
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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 | 0.001 |
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".