title: Obesity-related systemic factors promote an invasive phenotype in prostate cancer cells.
abstract: BACKGROUND
  Obesity is associated with larger tumors, shorter time to PSA failure, and higher Gleason scores. However, the mechanism(s) by which obesity promotes aggressive prostate cancer remains unknown. We hypothesize that circulating factors related to obesity promote prostate cancer progression by modulating components of the metastatic cascade.
  
  
  METHODS
  Male C57BL/6 mice (6 weeks) were fed an ad libitum diet-induced obesity (60% fat) or control diet (10% fat) for 12 weeks. Serum was collected, metabolic and inflammatory proteins were measured by an antibody array. Sera were used to measure, in vitro, characteristics of a metastatic phenotype.
  
  
  RESULTS
  Comparable to obese men, obese sera contained higher levels or leptin, vascular endothelial growth factor, PAI-1, interleukin-6 (IL-6) and lower levels of testosterone. In prostate cells, serum was used to assess: proliferation, invasion, migration, epithelial-mesenchymal-transition (EMT) and matrix metalloproteinase (MMP) activity. LNCaP and PacMetUT1 cells exposed to obese sera increased proliferation, whereas PrEC and DU145 were unaffected. LNCaP, PacMetUT1 and DU145 cancer cells exposed to obese sera resulted in increased invasion, migration and MMP-9 activity. Prostate cancer cells exposed to obese sera showed increased vimentin, dispersion of e-cadherin and β-catenin from the plasma membrane.
  
  
  CONCLUSIONS
  We report, prostate cancer cells exposed to sera from obese mice increases proliferation, invasion, migration, MMP activity and induces changes in proteins critical for EMT.
authors.affiliation: Department of Nutritional Sciences, The University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Price
authors.forename: D A
authors.initials: DA
authors.lastname: Cavazos
authors.forename: R E
authors.initials: RE
authors.lastname: De Angel
authors.forename: S D
authors.initials: SD
authors.lastname: Hursting
authors.forename: L A
authors.initials: LA
authors.lastname: deGraffenried
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009362:Neoplasm Metastasis; D009765:Obesity / Q000097:blood* / Q000150:complications; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology*; D013739:Testosterone / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D015850:Interleukin-6; D020738:Leptin; D017395:Plasminogen Activator Inhibitor 1; D042461:Vascular Endothelial Growth Factor A; D013739:Testosterone; D020780:Matrix Metalloproteinase 9