title: Tumor cell-educated periprostatic adipose tissue acquires an aggressive cancer-promoting secretory profile.
abstract: OBJECTIVE
  The microenvironment produces important factors that are crucial to prostate cancer (PCa) progression. However, the extent to which the cancer cells stimulate periprostatic adipose tissue (PPAT) to produce these proteins is largely unknown. Our purpose was to determine whether PCa cell-derived factors influence PPAT metabolic activity.
  
  
  METHODS
  Primary cultures of human PPAT samples from PCa patients (adipose tissue organotypic explants and primary stromal vascular fraction, SVF) were stimulated with conditioned medium (CM) collected from prostate carcinoma (PC3) cells. Cultures without CM were used as control. We used multiplex analysis and ELISA for protein quantification, qPCR to determine mitochondrial DNA (mtDNA) copy number and zymography for matrix metalloproteinase activity, in order to evaluate the response of adipose tissue explants and SVFs to PC3 CM.
  
  
  RESULTS
  Stimulation of PPAT explants with PCa PC3 CM induced adipokines associated with cancer progression (osteopontin, tumoral necrosis factor alpha and interleukin-6) and reduced the expression of the protective adipokine adiponectin. Notably, osteopontin protein expression was 13-fold upregulated. Matrix metalloproteinase 9 activity and mitochondrial DNA copy number were higher after stimulation with cancer CM. Stromovascular cells from PPAT in culture were not influenced by tumor-derived factors.
  
  
  CONCLUSIONS
  The modulation of adipokine expression by tumor CM indicates the pervasive extent to which tumor cells command PPAT to produce factors favorable to their aggressiveness.
authors.affiliation: Molecular Oncology Group-CI, Portuguese Institute of Oncology, Porto, Portugal. oriebir.r@gmail.com
authors.forename: Ricardo J T
authors.initials: RJ
authors.lastname: Ribeiro
authors.forename: Cátia P D
authors.initials: CP
authors.lastname: Monteiro
authors.forename: Virginia F P M
authors.initials: VF
authors.lastname: Cunha
authors.forename: Andreia S M
authors.initials: AS
authors.lastname: Azevedo
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Oliveira
authors.forename: Rosário
authors.initials: R
authors.lastname: Monteiro
authors.forename: Avelino M
authors.initials: AM
authors.lastname: Fraga
authors.forename: Paulo
authors.initials: P
authors.lastname: Príncipe
authors.forename: Carlos
authors.initials: C
authors.lastname: Lobato
authors.forename: Francisco
authors.initials: F
authors.lastname: Lobo
authors.forename: António
authors.initials: A
authors.lastname: Morais
authors.forename: Vitor
authors.initials: V
authors.lastname: Silva
authors.forename: José
authors.initials: J
authors.lastname: Sanches-Magalhães
authors.forename: Jorge
authors.initials: J
authors.lastname: Oliveira
authors.forename: João T
authors.initials: JT
authors.lastname: Guimarães
authors.forename: Carlos M S
authors.initials: CM
authors.lastname: Lopes
authors.forename: Rui M
authors.initials: RM
authors.lastname: Medeiros
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D053495:Osteopontin / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D052242:Adiponectin; D017077:Culture Media, Conditioned; D016207:Cytokines; D004272:DNA, Mitochondrial; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D053495:Osteopontin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9