Abstract 2562: EGCG targeting of adipogenesis reveals a STAT3-mediated paracrine oncogenic control of triple-negative breast cancer cell invasive phenotype

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.