Per- and Polyfluoroalkyl Substance Exposure Combined with High-Fat Diet Supports Prostate Cancer Progression

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, 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. Our studies are the first in the field to provide new and clinically relevant insights regarding novel metabolic and epigenetic states and support 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. Overall design: 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.

全氟和多氟烷基物质（Per- and polyfluoroalkyl substances, PFAS）是一类广泛应用于多种工业场景的合成化学品，涵盖阻燃剂、人工成膜泡沫、化妆品、不粘炊具等各类产品。流行病学研究表明，血液PFAS水平升高与前列腺癌发病率升高存在关联，但PFAS影响癌症发生发展的具体机制仍不明确。
为探究PFAS与前列腺癌之间的关联，本研究评估了高脂饮食联合PFAS暴露所引发的代谢改变对前列腺肿瘤进展的影响。本研究为该领域首次针对新型代谢与表观遗传状态提供了兼具创新性与临床相关性的见解，并为PFAS诱导型前列腺癌的有效预防与治疗策略的后续开发提供了支撑。本研究结果加深了对PFAS如何与高脂饮食协同促进前列腺癌发生的理解，并为减轻PFAS暴露奠定了重要基础。
整体实验设计：本研究通过构建暴露于全氟辛烷磺酸（Perfluorooctane sulfonate, PFOS，一种PFAS类化合物）的体内前列腺癌异种移植模型，并设置不同饮食干预组，以研究PFAS对前列腺癌进展及代谢活性的影响。研究采用代谢组学与转录组学技术，解析PFAS暴露后代谢谱的整体变化。此外，本研究还评估了良性细胞与肿瘤细胞中的代谢改变，这类代谢改变可引发表观基因组重编程与信号通路异常，最终增加肿瘤致瘤风险与侵袭性。