Abstract PR10: Cause and effect relationships between glycation and the ancestry specific tumor stroma
Authors: Lloyd Courtney E. , Krsianits Bradley A. , Woods Pamela , Foster Dion , Nogueira Lourdes M. , Sanders Bria , Spruill Laura , Ford Marvella E. , Ahmed Mahtabbudin , Findlay Victoria J. , Turner David P. 
Published: December 2020

Advanced glycation end products (AGEs) are reactive sugar metabolites that our research has shown can increase cancer severity. AGEs are formed endogenously via a slow, nonenzymic reaction. However, high AGE levels associate with the same socioeconomic and environmental factors that contribute to cancer health disparity. Lack of exercise and modern dietary patterns represent cancer disparity factors that lead to the increased accumulation of AGEs. Our published research indicates that AGE levels are highest in prostate cancer patients with more aggressive disease and those with African Ancestry. An accumulation of AGEs in the body drives chronic inflammation which has an impact on the progression of diseases such as Alzheimer’s, diabetes, and as we have recently shown cancer. Our unpublished data demonstrate that consumption of a diet high in AGEs increases the growth of prostate cancer in both syngeneic xenograft and spontaneous mouse models. Dietary-AGE mediated effects on prostate tumor growth were dependent upon the stromal expression of the receptor for AGE (RAGE) which led to the activation of fibroblasts. As part of a funded study (NIH/NCI: PQ3-R21CA194469 PI: Turner), we generated primary fibroblast and epithelial cell lines from Gleason 7 radical prostatectomy tissues donated by AA and EA men. Gleason 7 tumors represent a critical transition point in prostate cancer progression. Cells were molecularly characterized, confirmed as novel by STR analysis and percent ancestry confirmed. We performed two-compartment co-culture migration models with the ancestry specific primary cell lines. Compared to the corresponding experiment in EA men, we found that the presence of primary fibroblasts from AA men significantly increased the migratory potential of patient matched epithelial cells. We also examined the effects on epithelial cell migration when the ancestry specific stromal cells were cross-cultured. Compared to patient matched fibroblasts, the migratory potential of EA epithelial cells was significantly higher when cross-cultured with fibroblasts isolated from AA men. In contrast, the migratory potential of AA epithelial cells was significantly reduced when cross-cultured with EA fibroblasts. In both cases, the effects on epithelial cell migration was exacerbated when the ancestry specific fibroblasts were treated with exogenous AGE with the highest effects being observed with AA derived fibroblasts. The dietray-AGE mediated regulation of the tumor stroma in AA men with prostate cancer indicates an ancestry specific destablization of the tumor microenvironment supportive for aggressive disease. AGEs may represent a biological consequence of cancer disparity factors that can contibute to the increased prostate cancer incidence and mortality observed in men with African ancestry.

Citation Format: Courtney E. Lloyd, Bradley A. Krsianits, Pamela Woods, Dion Foster, Lourdes M. Nogueira, Bria Sanders, Laura Spruill, Marvella E. Ford, Mahtabbudin Ahmed, Victoria J. Findlay, David P. Turner. Cause and effect relationships between glycation and the ancestry specific tumor stroma [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PR10.