The impact of obesity on prostate cancer progression

textThe link between obesity and the risk of prostate cancer (PCa) is inconclusive. However, studies demonstrate a correlation between obesity, advanced PCa and mortality. Investigating the underlying biological mechanisms by which obesity promotes advanced PCa is necessary to develop potential therapeutic targets that may aid in the efficacy of treating obese men. Obesity-associated changes in tumor biology may modulate key aspects of the hallmarks of cancer; acquisition of characteristics essential for the development and progression of cancer. We hypothesized obesity-induced inflammation promotes PCa progression. Our studies incorporated cell culture and murine models to investigate the role of obesity-related systemic factors on AR signaling, inflammation-stimulated invasive PCa, and the paracrine interaction of the tumor-microenvironment (TME). We sought to recapitulate the systemic effects of obesity to investigate characteristics of the metastatic cascade. Briefly, sera from mice fed 60% or 10% kcal from fat diet for 12 weeks were used for in vitro studies. PCa cells exposed to sera from obese mice increased AR transcriptional activity, proliferation, invasion, migration, MMP-9 activity and EMT: e-cadherin, vimentin and β-catenin. PCa cells exposed to sera from 1 hour maintained the invasive phenotypes similar to PCa cells directly exposed to sera from obese mice. IL-6 is associated with advanced PCa cancer. Depleting sera of IL-6 or IL-6 shRNA suppressed obesity-induced proliferation, invasion, migration and MMP-9 activity in LNCaP cells. Furthermore, in a PTEN spontaneous model of PCa, IL-6 protein and mRNA levels corresponded with progression of PCa in mice fed a high-fat diet. These results suggest IL-6 mediates obesity-induced PCa progression. Stromal cells that comprise the TME vary in their contribution to the growth of tumors. Our studies show macrophage-like and myofibroblasts increased NF-kB activity in PCa cells exposed to sera from obese mice. An increase in NF-kB activity corresponded with proliferation, prostaglandin E2, and invasion and recruitment of stromal cells by PCa cells. In summary, obesity-related systemic factors promote an invasive PCa phenotype, which may be mediated by Akt, AR, IL-6 and the TME. Obesity-induced changes in tumor biology and the microenvironment provide a niche suitable for invasive prostate cancer.Nutritional Science

The role of Visfatin and Resistin in an In Vitro Model of Obesity-Induced Invasive Liver Cancer

Background: Obesity is associated with the development of liver disease and its progression to hepatocellular carcinoma. This link may be attributed to adipocytokines such as growth visfatin, and resistin which have been shown to promote liver cancer incidence and progression. Studies have yet to determine the role of visfatin and resistin in liver cancer specifically in the context of obesity. The objective of this study was to investigate the effect of neutralizing visfatin and resistin in obese (OB) or normal weight (NW) sera to determine the contribution of these proteins in obesity-induced invasive liver cancer. Methods: Sera from OB or NW males was used to determine the efficacy of neutralizing visfatin and resistin to reduce the obesity-induced liver cancer phenotype. HepG2 and SNU-449 cells were exposed to OB and NW sera antibodies for visfatin or resistin. The neutralizing antibodies differentially suppressed invasion, ROS production, and matrix metalloproteinase-9 secretion. These changes corresponded with a decrease in phosphorylated ERK and Akt in HepG2 cells, but differences were not observed in CAP1 or β-catenin. In conclusion, visfatin and resistin have differential roles in obesity-associated liver cancer and may be potential targets to reverse the impact of obesity on liver cancer progression.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

A Scoping Review to Explore the Potential Benefits of Nutrition Interventions for Latino/a Adult Cancer Survivors in the US

Despite evidence for the role of healthy diets in preventing cancer, little is known about how nutrition can support positive health outcomes after a cancer diagnosis for Latino/a cancer survivors in the United States (U.S.). The purpose of this scoping review is to understand the potential benefits of nutrition interventions in supporting healthy survivorship among Latino/a cancer survivors in the U.S. A team compiled, evaluated, and summarized the available evidence. Potentially relevant studies were identified from a comprehensive search of peer-reviewed databases and the gray literature. Eligible studies included Latino/a adult cancer survivors with a nutrition education, dietary change, or behavioral intervention; and a nutrition-related health outcome. Data were extracted and summarized using tables. The review included 10 randomized controlled trials, with samples or subsamples of Latino/a cancer survivors. Interventions mostly focused on breast cancer survivors. The results showed some evidence that dietary behaviors, like fruit and vegetable intake, were related to positive outcomes, like a decreased risk of cancer (through changes in DNA methylation), decreased risk breast cancer recurrence (through changes in inflammatory biomarkers), or improved perception of health status. The findings highlight a need for community-engaged and culturally relevant nutrition interventions for Latino/a adults, especially for rural communities; and innovative intervention approaches, including m/ehealth approaches with long-term follow-up