Whole genome analyses support the tumor stroma as the main site of molecular change that
promotes deadly prostate cancer in African American men. However, complimentary basic
research studies showing a direct cause-and-effect relationship are lacking.
As our bodies use the sugars, we consume for energy they generate waste chemicals known
as metabolites. One such group of metabolites is known as advanced glycation end products or
AGEs for short. AGE accumulation in our tissues and organs causes their functional decline and
accelerates the aging process. AGEs represent intrinsic biological elements within health disparity
risk factors that align with the stromal profiles that influence prostate cancer in African American
men. This group has previously shown that AGEs are elevated in the circulation and tumors of
prostate cancer patients with highest levels being observed in men with African ancestry and in
more aggressive tumors. Using diet as a surrogate for health inequity, a key and novel finding from
this research is that dietary consumption of AGEs can directly accelerate prostate tumor growth.
Dietary-AGE mediated effects on tumor growth were shown to be dependent upon stromal
signaling by the transmembrane receptor for AGE (RAGE). AGE-RAGE signaling was associated
with an activated stroma similar to that observed in African American men with prostate cancer.
This was defined by the increased presence of cancer associated fibroblasts (CAFs) and the
downregulation of matrix associated genes.
The long-term, objective is to integrate ancestral tumor biology into the multilevel framework of
health inequity constructs to inform on cancer disparity outcomes. The study hypothesis is that
“increased AGE bioavailability contributes to rapid tumor progression in AA men with PCa
cancer”. The study will use a combination of prostate cancer cell lines and unique mouse tumor
models to define a direct cause-and-effect relationship between AGEs and ancestry specific
crosstalk in the tumor associated stroma. It will also assess if the consumption of AGEs has a
positive correlation with prostate cancer risk using data from large human cohort studies.
By establishing the mechanistic consequences AGEs found in the food chain on ancestry
specific tumor biology, defined strategies to limit their accumulation in at risk populations, such as
African American men with prostate cancer, may be viewed as cancer preventive or therapeutic
strategies when combined with existing treatment regimens.