title: Soluble gp130 regulates prostate cancer invasion and progression in an interleukin-6 dependent and independent manner.
abstract: OBJECTIVE
  Soluble gp130 is a regulator of interleukin-6/soluble interleukin-6 receptor signaling that influences prostate cancer progression. We determined the association of soluble gp130 with prostate cancer prognosis, invasiveness and epithelial-to-mesenchymal transition.
  
  
  METHODS
  A total of 423 preoperative and 206 postoperative blood samples were available from patients treated with radical prostatectomy for clinically localized prostate cancer. Prostate cancer cell lines were used for in vitro studies. Plasma soluble gp130, interleukin-6 and soluble interleukin-6 receptor levels were measured using enzyme immunoassay. In vitro invasion assays and quantification of E-cadherin expression were done using modified Boyden chambers and Western blot, respectively.
  
  
  RESULTS
  In patients treated with radical prostatectomy higher preoperative plasma soluble gp130 was significantly associated with higher biopsy and pathological Gleason sum, extraprostatic extension, seminal vesicle invasion, lymph node metastasis and biochemical recurrence. In a subset of 206 patients postoperative soluble gp130 levels were 18% lower than preoperative levels (p = 0.037). Soluble gp130 levels weakly correlated with preoperative plasma interleukin-6 and soluble interleukin-6 receptor levels. In vitro soluble gp130 alone increased the invasiveness of androgen responsive prostate cancer cells and induced a significant decrease in E-cadherin. In patients higher plasma soluble gp130 was associated with features of biologically aggressive prostate cancer. The decrease in postoperative plasma soluble gp130 after surgery suggests that the higher blood levels of soluble gp130 are produced by tumor cells.
  
  
  CONCLUSIONS
  Data suggest that soluble gp130 has a role in prostate cancer invasion in an interleukin-6 dependent and independent manner.
authors.affiliation: Division of Medical Oncology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, New York, USA.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Chromecki
authors.forename: Julia
authors.initials: J
authors.lastname: Hoefer
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Barbieri
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Scherr
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
authors.forename: Claus G
authors.initials: CG
authors.lastname: Roehrborn
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.forename: Zoran
authors.initials: Z
authors.lastname: Culig
authors.forename: Ilaria T
authors.initials: IT
authors.lastname: Cavarretta
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D015153:Blotting, Western; D015820:Cadherins / Q000097:blood; D045744:Cell Line, Tumor; D050822:Cytokine Receptor gp130 / Q000097:blood / Q000502:physiology*; D018450:Disease Progression; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000502:physiology*; D016015:Logistic Models; D008207:Lymphatic Metastasis; D008297:Male; D009361:Neoplasm Invasiveness; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D019947:Receptors, Interleukin-6 / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130