Division of Nutritional Sciences, University of Illinois, Urbana-Champaign, Urbana, IL 61801, USA.
Department of Food Science and Human Nutrition, University of Illinois, Urbana-Champaign, Urbana, IL 61801, USA.
Nutrients. 2021 Oct 30;13(11):3902. doi: 10.3390/nu13113902.
Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals utilized in various industrial settings and include products such as flame retardants, artificial film-forming foams, cosmetics, and non-stick cookware, among others. Epidemiological studies suggest a link between increased blood PFAS levels and prostate cancer incidence, but the mechanism through which PFAS impact cancer development is unclear. To investigate the link between PFAS and prostate cancer, we evaluated the impact of metabolic alterations resulting from a high-fat diet combined with PFAS exposure on prostate tumor progression. We evaluated in vivo prostate cancer xenograft models exposed to perfluorooctane sulfonate (PFOS), a type of PFAS compound, and different diets to study the effects of PFAS on prostate cancer progression and metabolic activity. Metabolomics and transcriptomics were used to understand the metabolic landscape shifts upon PFAS exposure. We evaluated metabolic changes in benign or tumor cells that lead to epigenomic reprogramming and altered signaling, which ultimately increase tumorigenic risk and tumor aggressiveness. Our studies are the first in the field to provide new and clinically relevant insights regarding novel metabolic and epigenetic states as well as to support the future development of effective preventative and therapeutic strategies for PFAS-induced prostate cancers. Our findings enhance understanding of how PFAS synergize with high-fat diets to contribute to prostate cancer development and establish an important basis to mitigate PFAS exposure.
全氟和多氟烷基物质（PFAS）是广泛应用于各种工业领域的合成化学物质，包括阻燃剂、人工成膜泡沫、化妆品和不粘炊具等产品。流行病学研究表明，血液中 PFAS 水平升高与前列腺癌发病率之间存在关联，但 PFAS 影响癌症发展的机制尚不清楚。为了研究 PFAS 与前列腺癌之间的联系，我们评估了高脂肪饮食与 PFAS 暴露相结合所导致的代谢改变对前列腺肿瘤进展的影响。我们评估了暴露于全氟辛烷磺酸（PFOS）等 PFAS 化合物的前列腺癌异种移植模型和不同饮食，以研究 PFAS 对前列腺癌进展和代谢活性的影响。我们使用代谢组学和转录组学来了解 PFAS 暴露后代谢景观的变化。我们评估了良性或肿瘤细胞中的代谢变化，这些变化导致表观基因组重编程和信号改变，最终增加了肿瘤发生风险和肿瘤侵袭性。我们的研究首次提供了关于新型代谢和表观遗传状态的新的、具有临床相关性的见解，并为未来开发针对 PFAS 诱导的前列腺癌的有效预防和治疗策略提供了支持。我们的发现增强了对 PFAS 如何与高脂肪饮食协同作用导致前列腺癌发展的理解，并为减轻 PFAS 暴露奠定了重要基础。
