Biological and clinical significance of the AGE-RAGE axis in the aggressiveness and prognosis of prostate cancer

Shih-Hong Khoo^a†, Pei-Ru Wu ^b,c†, Kun-Tu Yeh^c,d,e, Shih-Lan Hsu^f and Chi-Hao Wu^g*

^aSchool of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 110301, Taiwan

^bDepartment of Pathology, Cheng-Ching General Hospital, Taichung 40764, Taiwan

^cDepartment of Surgical Pathology, Changhua Christian Hospital, Changhua 50006, Taiwan

^dSchool of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan

^eDepartment of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 40227, Taiwan

^fDepartment of Medical Research, Taichung Veterans General Hospital, Taichung 40705, Taiwan

^gGraduate Program of Nutrition Science, School of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan

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.

Keywords: Advanced glycation end products, Aggressiveness, Glycative stress, Prostate cancer, RAGE

https://doi.org/10.38212/2224-6614.3475