Mechanistic Insights into the Link between Obesity and Prostate Cancer

Abstract

Obesity is a pandemic of increasing worldwide prevalence. There is evidence of an association between obesity and the risk of prostate cancer from observational studies, and different biologic mechanisms have been proposed. The chronic low-level inflammation within the adipose tissue in obesity results in oxidative stress, activation of inflammatory cytokines, deregulation of adipokines signaling, and increased circulating levels of insulin and insulin-like growth factors (IGF). These mechanisms may be involved in epithelial to mesenchymal transformation into a malignant phenotype that promotes invasiveness, aggressiveness, and metastatic potential of prostate cancer. A thorough understanding of these mechanisms may be valuable in the development of effective prostate cancer prevention strategies and treatments. This review provides an overview of these mechanisms.

Dysregulation of the miRNome unveils a crosstalk between obesity and prostate cancer: miR-107 asa personalized diagnostic and therapeutic tool

“…Indeed, miR-107 also allowed a strong discriminatory capacity between SigPCa and NonSigPCa in obese PCa patients, thus representing not only a diagnostic but also a potential prognostic biomarker in that an obesity condition has been reported to represent a risk factor for PCa development, aggressiveness, and mortality. 43,44 Altogether, our results provide new, compelling evidence supporting the contention that miR-107 represents a promising diagnostic, prognostic, and/or therapeutic tool, worth to be further explored, in the pathological association between PCa and obesity.…”

Construction and validation of a clinical predictive nomogram for intraductal carcinoma of the prostate based on Chinese multicenter clinical data

“…This state leads to decreased cancer cell apoptosis and increased cancer cell growth and migration. Thus, these multiple factors may work in tandem to create a favorable tumor microenvironment for PCa cell growth in the catheter ( 34 ). Obesity has also been associated with insulin and sex hormone levels as well as the insulin-like growth factor axis.…”

Role of adipocyte browning in prostate and breast tumor microenvironment

“…The mechanisms connecting adiposity and the progression of PC are poorly understood, and may be multifactorial[ 40 ]. In this respect, prospective components consisting of adipokine signaling pathways, sex hormone concentrations, and variation along the insulin/insulin-like-growth-factor (IGF) axis were involved[ 41 42 ]. (1) In adipokine signaling pathways, leptin and adiponectin are the two most plentiful and well-studied adipokines.…”

“…Insulin increases cell proliferation and glucose consumption in PC cells but not in noncancerous prostate epithelial cells[ 55 ]. The IGF-axis is composed of cell surface receptors, ligands, IGF-binding proteins, and proteases[ 41 ]. Epidemiological studies have shown that higher serum IGF-1 concentrations and downregulated circulating IGFBP-3 levels are correlated with an increased risk of developing PC[ 56 ].…”