TY - JOUR
T1 - Soluble gp130 regulates prostate cancer invasion and progression in an interleukin-6 dependent and independent manner
AU - Shariat, Shahrokh F.
AU - Chromecki, Thomas F.
AU - Hoefer, Julia
AU - Barbieri, Christopher E.
AU - Scherr, Douglas S.
AU - Karakiewicz, Pierre I.
AU - Roehrborn, Claus
AU - Montorsi, Francesco
AU - Culig, Zoran
AU - Cavarretta, Ilaria T.
N1 - Funding Information:
Supported by Austrian Science Fund FWF Grant W1101 (ZC).
PY - 2011/11
Y1 - 2011/11
N2 - Purpose: 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. Materials and 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.
AB - Purpose: 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. Materials and 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.
KW - biological markers
KW - cytokine receptor gp130
KW - neoplasm invasiveness
KW - prostate
KW - prostatic neoplasms
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U2 - 10.1016/j.juro.2011.06.048
DO - 10.1016/j.juro.2011.06.048
M3 - Article
C2 - 21944124
AN - SCOPUS:80053953454
SN - 0022-5347
VL - 186
SP - 2107
EP - 2114
JO - Journal of Urology
JF - Journal of Urology
IS - 5
ER -