Abstract 2562: EGCG targeting of adipogenesis reveals a STAT3-mediated paracrine oncogenic control of triple-negative breast cancer cell invasive phenotype
Bibliographic record
Abstract
Abstract Background: Obese subjects have an increased risk of developing triple-negative breast cancer (TNBC), in part associated with the chronic low-grade inflammation state. On the other hand, epidemiological data indicates that increased consumption of polyphenol-rich fruits and vegetables plays a key role in reducing incidence of some cancers. Objectives: Here, we tested whether green tea-derived epigallocatechin-3-gallate (EGCG) could alter adipogenesis involved in the maturation of pre-adipocytes, and how this impacts the paracrine regulation of the mature adipocytes secretome on the TNBC invasive phenotype. Methods: Differentiation was performed and conditioned media (CM) from preadipocytes and mature adipocytes harvested. Human TNBC-derived MDA-MB-231 real-time cell migration was performed using the exCELLigence system. Differential gene arrays and RT-qPCR were used to assess gene expression levels. Western blotting was used to assess protein expression levels. In vitro vasculogenic mimicry (VM) was assessed with Matrigel. Results: EGCG was found to inhibit the induction of numerous key adipogenic biomarkers, including lipoprotein lipase, adiponectin, leptin, fatty acid synthase, and fatty acid binding protein 4. Increased MDA-MB-231 chemotaxis and VM were found in response to mature adipocytes secretome, and this was correlated with the induction of the STAT3 signaling pathway. This invasive phenotype was prevented by EGCG, JAK/STAT inhibitors Tofacitinib and AG490, as well as upon STAT3 gene silencing. Conclusion: Adipocytes secretome plays a key role in the paracrine regulation of TNBC cells invasive phenotype. Dietary catechin-mediated interventions may, in part through the inhibition of adipogenesis and modulation of adipocytes secretome, prevent the onset of an obesogenic environment that favors TNBC development. Citation Format: Narjara Gonzalez Suarez, Sahily Rodriguez Torres, Borhane Annabi. EGCG targeting of adipogenesis reveals a STAT3-mediated paracrine oncogenic control of triple-negative breast cancer cell invasive phenotype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2562.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".