Tumor expression of adiponectin receptor 2 and lethal prostate cancer

Abstract

To investigate the role of adiponectin receptor 2 (AdipoR2) in aggressive prostate cancer we used immunohistochemistry to characterize AdipoR2 protein expression in tumor tissue for 866 men with prostate cancer from the Physicians' Health Study and the Health Professionals Follow-up Study. AdipoR2 tumor expression was not associated with measures of obesity, pathological tumor stage or prostate-specific antigen (PSA) at diagnosis. However, AdipoR2 expression was positively associated with proliferation as measured by Ki-67 expression quartiles (P-trend < 0.0001), with expression of fatty acid synthase (P-trend = 0.001), and with two measures of angiogenesis (P-trend < 0.1). An inverse association was observed with apoptosis as assessed by the TUNEL assay (P-trend = 0.006). Using Cox proportional hazards regression and controlling for age at diagnosis, Gleason score, year of diagnosis category, cohort and baseline BMI, we identified a statistically significant trend for the association between quartile of AdipoR2 expression and lethal prostate cancer (P-trend = 0.02). The hazard ratio for lethal prostate cancer for the two highest quartiles, as compared to the two lowest quartiles, of AdipoR2 expression was 1.9 (95% confidence interval [CI]: 1.2-3.0). Results were similar when additionally controlling for categories of PSA at diagnosis and Ki-67 expression quartiles. These results strengthen the evidence for the role of AdipoR2 in prostate cancer progression.

Cholesterol Metabolism and Prostate Cancer Lethality

“…Cell proliferation was measured with tissue microarrays for the Ki-67 antigen of proliferating cells, as previously described (19). …”

The role of tumor metabolism as a driver of prostate cancer progression and lethal disease: results from a nested case-control study

“…The HPFS [12] is a cohort study initiated in 1986 among 51,529 male health professionals aged 40 to 75 years. The PHS [13–15] was initiated as a randomized trial of aspirin and beta-carotene for the primary prevention of cardiovascular disease and cancer among 22,071 US male physicians aged 40 to 84 years.…”

Fortifying the Treatment of Prostate Cancer with Physical Activity

“…AMPK activation by adiponectin has been shown to inhibit prostate and colon cancer cell viability [ 57 ] but paradoxically also enhanced prostate cancer cell migration and metastatic potential [ 58 ]. Adding to this controversy, Rider et al recently found that high expression of the adiponectin receptor 2 in prostate tumors was associated with increased proliferation and worse survival but was not associated with BMI or PSA levels [ 59 ]. The role of exercise-induced AMPK activation in prostate cancer therefore remains somewhat speculative, while the metabolic benefits of global upregulation of AMPK remain clearer.…”