White adipose tissue-derived factors and prostate cancer progression: mechanisms and targets for interventions

Obesity represents an important risk factor for prostate cancer, driving more aggressive disease, chemoresistance, and increased mortality. White adipose tissue (WAT) overgrowth in obesity is central to the mechanisms that lead to these clinical observations. Adipose stromal cells (ASCs), the progenitors to mature adipocytes and other cell types in WAT, play a vital role in driving PCa aggressiveness. ASCs produce numerous factors, especially chemokines, including the chemokine CXCL12, which is involved in driving EMT and chemoresistance in PCa. A greater understanding of the impact of WAT in obesity-induced progression of PCa and the underlying mechanisms has begun to provide opportunities for developing interventional strategies for preventing or offsetting these critical events. These include weight loss regimens, therapeutic targeting of ASCs, use of calorie restriction mimetic compounds, and combinations of compounds as well as specific receptor targeting strategies.