(P13-043-23) Nutrition Derived Advanced Glycation End Products Are Bio-Social Determinants of Health That Inform on Cancer Disparities

Objectives: Through their ability to perpetuate a reactive stroma, the objective was to define the increased nutritional bioavailability of advanced glycation end products (AGEs) as a pro-tumorigenic consequence of interrelated health inequity risk factors that can influence ancestry specific tumor biology.

Methods: In vivo, ex vivo, and in vitro models were used to define the molecular effects of nutrition associated AGEs on the ancestry specific tumor microenvironment and tumor growth.

Results: The PI’s work provides the first in vivo evidence supporting an oncogenic role for AGEs. In mouse allograft models, both the chronic consumption of AGEs and pre-treatment with AGE bound peptide (p < 0.0001) increased prostate tumor growth. In spontaneous tumor models, chronic AGE consumption caused rapid disease progression through prostate intra-epithelial neoplasia (p=0.049) to adenocarcinoma and metastatic disease. Mechanistically, AGEs recapitulated a regulatory program of ‘activated’ stroma similar to that observed in African American prostate tumors. Specifically, increased AGE bioavailability caused receptor for AGE (RAGE) dimerization in resident PCa fibroblasts leading to their activation and the downregulation of matrix regulatory proteins leading to rapid tumor progression.

Conclusions: When social and biological determinants of health are compromised it may increase nutritional exposure to AGEs and perpetuate a vicious cycle of AGE formation, bioavailability, and pathogenicity. As bio-social determinants of health, AGEs may represent informative and/or functional biomarkers that can be utilized across transdisciplinary studies to address the enduring complexities of cancer disparity.

Funding Sources: NIH/NCI, Massey Cancer Center, Bobzilla Foundation