title: Periprostatic adipose tissue as a modulator of prostate cancer aggressiveness.
abstract: OBJECTIVE
  Adipose tissue has been suggested to contribute to the pathogenesis of various disease states, including prostate cancer. We investigated the association of cytokines and growth factors secreted by periprostatic adipose tissue with pathological features of aggressive prostate cancer.
  
  
  METHODS
  Periprostatic adipose tissue was harvested from patients undergoing radical prostatectomy and cultured for 24 hours to generate conditioned medium or snap frozen immediately for functional signaling profiling. Multiplex analysis of the periprostatic adipose tissue conditioned medium was used to detect cytokine levels and compared to patient matched serum from 7 patients. Interleukin-6 in serum and periprostatic adipose tissue conditioned medium was further analyzed by enzyme-linked immunosorbent assay and correlated with clinical variables, such as age, body mass index and Gleason score, in 45 patients. Interleukin-6 expression in periprostatic adipose tissue was determined by immunohistochemistry. Reverse phase protein microarray technology was used to analyze cell signaling networks in periprostatic adipose tissue.
  
  
  RESULTS
  Interleukin-6 in periprostatic adipose tissue conditioned medium was approximately 375 times greater than that in patient matched serum and levels correlated with pathological grade. This finding was further extended by cell signaling analysis of periprostatic adipose tissue, which showed greater phosphorylation on Stat3 with high grade tumors (any component of Gleason score 4 or 5).
  
  
  CONCLUSIONS
  Higher Gleason score correlated with high levels of conditioned medium derived interleukin-6. Moreover, cell signaling analysis of periprostatic adipose tissue identified activated signaling molecules, including STAT3, that correlated with Gleason score. Since STAT3 is interleukin-6 regulated, these findings suggest that periprostatic adipose tissue may have a role in modulating prostate cancer aggressiveness by serving as a source of interleukin-6. Also, we found low numbers of inflammatory cells in the fat, suggesting that adipocytes are the major secretors of interleukin-6.
authors.affiliation: Department of Urology, University of California-Irvine, Orange, California, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Finley
authors.forename: Valerie S
authors.initials: VS
authors.lastname: Calvert
authors.forename: Junichi
authors.initials: J
authors.lastname: Inokuchi
authors.forename: Alice
authors.initials: A
authors.lastname: Lau
authors.forename: Navneet
authors.initials: N
authors.lastname: Narula
authors.forename: Emanuel F
authors.initials: EF
authors.lastname: Petricoin
authors.forename: Frank
authors.initials: F
authors.lastname: Zaldivar
authors.forename: Rosanne
authors.initials: R
authors.lastname: Santos
authors.forename: Darren R
authors.initials: DR
authors.lastname: Tyson
authors.forename: David K
authors.initials: DK
authors.lastname: Ornstein
mesh_terms: D000273:Adipose Tissue / Q000737:chemistry / Q000378:metabolism*; D016207:Cytokines / Q000032:analysis / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000378:metabolism*; D015850:Interleukin-6 / Q000032:analysis / Q000378:metabolism; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology*
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6