Laboratoire d'Oncologie Moléculaire, Département de Chimie, Centre de Recherche CERMO-FC, Université du Québec à Montréal, Montréal, QC H3C 3P8, Canada.
Molecules. 2021 Mar 10;26(6):1506. doi: 10.3390/molecules26061506.
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 cancer types. Here, we tested whether green tea-derived epigallocatechin-3-gallate (EGCG) could alter adipose-derived mesenchymal stem cell differentiation into adipocytes, and how this impacts the secretome profile and paracrine regulation of the TNBC invasive phenotype. Here, cell 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 and phosphorylation status levels. In vitro vasculogenic mimicry (VM) was assessed with Matrigel. EGCG was found to inhibit the induction of key adipogenic biomarkers, including lipoprotein lipase, adiponectin, leptin, fatty acid synthase, and fatty acid binding protein 4. Increased TNBC-derived MDA-MB-231 cell chemotaxis and vasculogenic mimicry were observed in response to mature adipocytes secretome, and this was correlated with increased STAT3 phosphorylation status. This invasive phenotype was prevented by EGCG, the JAK/STAT inhibitors Tofacitinib and AG490, as well as upon STAT3 gene silencing. In conclusion, dietary catechin-mediated interventions could, in part through the inhibition of adipogenesis and modulation of adipocytes secretome profile, prevent the onset of an obesogenic environment that favors TNBC development.
肥胖受试者发生三阴性乳腺癌（TNBC）的风险增加，部分原因与慢性低度炎症状态有关。另一方面，流行病学数据表明，增加富含多酚的水果和蔬菜的消费在降低某些癌症类型的发病率方面起着关键作用。在这里，我们测试了绿茶来源的表没食子儿茶素没食子酸酯（EGCG）是否可以改变脂肪来源的间充质干细胞向脂肪细胞的分化，以及这如何影响 TNBC 侵袭表型的分泌组谱和旁分泌调节。在这里，进行了细胞分化，并收获了前体脂肪细胞和成熟脂肪细胞的条件培养基（CM）。使用 exCELLigence 系统进行了人 TNBC 衍生的 MDA-MB-231 实时细胞迁移。使用差异基因阵列和 RT-qPCR 评估基因表达水平。使用 Western blotting 评估蛋白质表达和磷酸化状态水平。在体外使用 Matrigel 评估血管生成模拟（VM）。发现 EGCG 抑制关键脂肪生成生物标志物的诱导，包括脂蛋白脂肪酶、脂联素、瘦素、脂肪酸合酶和脂肪酸结合蛋白 4。在成熟脂肪细胞分泌物的作用下，观察到 TNBC 衍生的 MDA-MB-231 细胞趋化性和血管生成模拟增加，这与 STAT3 磷酸化状态的增加相关。这种侵袭表型可通过 EGCG、JAK/STAT 抑制剂托法替尼和 AG490 以及 STAT3 基因沉默来预防。总之，饮食儿茶素介导的干预措施可能部分通过抑制脂肪生成和调节脂肪细胞分泌组谱，预防有利于 TNBC 发展的肥胖环境的发生。
