Obesity and prostate cancer. Role of adipocytokines and clinical implications

Obesity is proposed as a possible risk factor for many tumors. The present review discusses the current knowledge on the clinical and biological impact of obesity on the development and progression of prostate cancer, the role of adipocyte-derived hormones (adipocytokines) in this scenario and the resulting clinical implications. In addition, the results of own experimental and clinical studies on the involvement of adipocytokines (e. g. leptin, adiponectin) in the pathophysiology of prostate cancer are presented. It was found that patients who were diagnosed with prostate cancer at this clinic had higher serum leptin and lower serum adiponectin concentrations. These investigations and other studies have further shown that higher serum levels of the adipocytokine leptin were associated with larger prostate cancer volumes, high-grade classification, biochemical recurrence, metastasis and progression of metastatic prostate tumors, as well as increased mortality. Moreover, there was a strong correlation between the serum level of leptin and serum levels of prostate specific antigen (PSA). Leptin stimulated in vitro the proliferation and inhibited the apoptosis of prostate cancer cells in a dose and time-dependent manner, however, androgen-resistant cell lines responded more strongly. At the molecular level, adipocytokines require the network of tyrosine kinases to accomplish the mitogenic and antiapoptotic effects in prostate cancer cells. Prominent members of the most important signal transduction cascades, such as MAPK, PI3-K and JAK/STAT are activated upon binding of leptin to its receptor on the cell membrane of prostate cancer cells. Adipocytokines such as leptin may serve as additional prognostic parameters for the evaluation of specific therapies for metastatic hormone refractory prostate cancer. The findings presented here are intended as a basis for further studies.