title: Linking obesogenic dysregulation to prostate cancer progression.
abstract: The global epidemic of obesity is closely linked to the development of serious co-morbidities, including many forms of cancer. Epidemiological evidence consistently shows that obesity is associated with a similar or mildly increased incidence of prostate cancer but, more prominently, an increased risk for aggressive prostate cancer and prostate cancer-specific mortality. Studies in mice demonstrate that obesity induced by high-fat feeding increases prostate cancer progression; however, the mechanisms underpinning this relationship remain incompletely understood. Adipose tissue expansion in obesity leads to local tissue dysfunction and is associated with low-grade inflammation, alterations in endocrine function and changes in lipolysis that result in increased delivery of fatty acids to tissues of the body. The human prostate gland is covered anteriorly by the prominent peri-prostatic adipose tissue and laterally by smaller adipose tissue depots that lie directly adjacent to the prostatic surface. We discuss how the close association between dysfunctional adipose tissue and prostate epithelial cells might result in bi-directional communication to cause increased prostate cancer aggressiveness and progression. However, the literature indicates that several 'mainstream' hypotheses regarding obesity-related drivers of prostate cancer progression are not yet supported by a solid evidence base and, in particular, are not supported by experiments using human tissue. Understanding the links between obesity and prostate cancer will have major implications for the health policy for men with prostate cancer and the development of new therapeutic or preventative strategies.
authors.affiliation: Department of PhysiologyCancer Program and Obesity and Metabolic Disease Program, Biomedicine Discovery Institute, Monash University, Wellington Road, Victoria 3800, Australia renea.taylor@monash.edu matthew.watt@monash.edu.
authors.forename: Renea A
authors.initials: RA
authors.lastname: Taylor
authors.affiliation: Department of PhysiologyCancer Program and Obesity and Metabolic Disease Program, Biomedicine Discovery Institute, Monash University, Wellington Road, Victoria 3800, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lo
authors.affiliation: Department of PhysiologyCancer Program and Obesity and Metabolic Disease Program, Biomedicine Discovery Institute, Monash University, Wellington Road, Victoria 3800, Australia.
authors.forename: Natasha
authors.initials: N
authors.lastname: Ascui
authors.affiliation: Department of PhysiologyCancer Program and Obesity and Metabolic Disease Program, Biomedicine Discovery Institute, Monash University, Wellington Road, Victoria 3800, Australia renea.taylor@monash.edu matthew.watt@monash.edu.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Watt
keywords: adipose tissue; inflammation; lipid metabolism; obesity; prostate cancer