School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 110301, Taiwan.
Department of Pathology, Cheng-Ching General Hospital, Taichung 40764, Taiwan.
J Food Drug Anal. 2023 Dec 15;31(4):664-682. doi: 10.38212/2224-6614.3475.
Dietary factors and chronic hyperglycemia are linked to the formation of advanced glycation end products (AGEs) and prostate cancer (PCa) risk. The activation of the receptor for AGEs (RAGE) acts as a bridge between various RAGE ligands and certain malignancies. This study showed that the interaction of AGEs and RAGE promoted PCa cell proliferation, invasion, and autophagy-mediated survival in response to chemotherapeutic agents. RAGE-overexpressed PCa cells underwent epithelial-mesenchymal transition and showed increased cancer stem cell-like properties. In mouse xenograft models, RAGE-overexpressed cells showed more substantial tumorigenic capacity than parental cells, whereas RAGE knockdown decreased tumorigenicity. The clinical data validated a positive correlation between high AGE and RAGE expressions with poor clinical outcomes. Our findings suggest that the AGE-RAGE axis facilitates PCa progression and aggressiveness. Prostatic AGEs and RAGE expression levels are associated with PCa prognosis. Adherence to a reduced-AGE diet and targeting RAGE are potential approaches to complement and synergize with the current PCa therapies.
饮食因素和慢性高血糖与晚期糖基化终产物 (AGEs) 的形成和前列腺癌 (PCa) 风险有关。AGEs 的受体 (RAGE) 的激活充当了各种 RAGE 配体与某些恶性肿瘤之间的桥梁。本研究表明，AGEs 和 RAGE 的相互作用促进了 PCa 细胞对化疗药物的增殖、侵袭和自噬介导的存活。RAGE 过表达的 PCa 细胞经历上皮-间充质转化，并表现出增加的癌症干细胞样特性。在小鼠异种移植模型中，RAGE 过表达的细胞显示出比亲本细胞更强的致瘤能力，而 RAGE 敲低则降低了致瘤性。临床数据验证了高 AGE 和 RAGE 表达与不良临床结果之间的正相关。我们的研究结果表明，AGE-RAGE 轴促进了 PCa 的进展和侵袭性。前列腺 AGEs 和 RAGE 表达水平与 PCa 的预后相关。遵循低 AGE 饮食和靶向 RAGE 可能是补充和协同当前 PCa 治疗的潜在方法。
