Expression of STAT3 in Prostate Cancer Metastases

被引：81

作者：

Don-Doncow, Nicholas ^{[1
]}

Marginean, Felicia ^{[1
,2
]}

Coleman, Ilsa ^{[3
]}

Nelson, Peter S. ^{[3
]}

Ehrnstrom, Roy ^{[2
]}

Krzyzanowska, Agnieszka ^{[1
]}

Morrissey, Colm ^{[4
]}

Hellsten, Rebecka ^{[1
]}

Bjartell, Anders ^{[1
,5
]}

机构：

[1] Lund Univ, Div Urol Canc, Dept Translat Med, Malmo, Sweden

[2] Skane Univ Hosp, Dept Pathol, Univ & Reg Labs, Malmo, Sweden

[3] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA

[4] Univ Washington, Dept Urol, Seattle, WA 98195 USA

[5] Lund Univ, Skane Univ Hosp, Dept Urol, Malmo, Sweden

来源：

EUROPEAN UROLOGY | 2017年 / 71卷 / 03期

基金：

瑞典研究理事会;

关键词：

Castration-resistant; Metastases; Prostate cancer; STAT3; Tissue microarray; ACTIVATION; RECEPTOR; CELLS; BONE;

D O I：

10.1016/j.eururo.2016.06.018

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

STAT3 and its upstream activator IL6R have been implicated in the progression of prostate cancer and are possible future therapeutic targets. We analyzed 223 metastatic samples from rapid autopsies of 71 patients who had died of castration-resistant prostate cancer (CRPC) to study protein and gene expression of pSTAT3 and IL6R. Immunohistochemical analysis revealed that 95% of metastases were positive for pSTAT3 and IL6R, with varying expression levels. Bone metastases showed significantly higher expression of both pSTAT3 and IL6R in comparison to lymph node and visceral metastases. STAT3 mRNA levels were significantly higher in bone than in lymph node and visceral metastases, whereas no significant difference in IL6R mRNA expression was observed. Our study strongly supports the suggested view of targeting STAT3 as a therapeutic option in patients with metastatic CRPC. Patient summary: We studied the levels of two proteins (pSTAT3 and IL6R) in metastases from patients who died from castration-resistant prostate cancer. We found high levels of pSTAT3and IL6R in bone metastases, suggesting that these proteins could be used as targets for new anticancer drugs. (C) 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

引用

页码：313 / 316

页数：4

共 10 条

[1] Tumour cell survival mechanisms in lethal metastatic prostate cancer differ between bone and soft tissue metastases [J].

Akfirat, Canan ;

Zhang, Xiaotun ;

Ventura, Aviva ;

Berel, Dror ;

Colangelo, Mary E. ;

Miranti, Cindy K. ;

Krajewska, Maryla ;

Reed, John C. ;

Higano, Celestia S. ;

True, Lawrence D. ;

Vessella, Robert L. ;

Morrissey, Colm ;

Knudsen, Beatrice S. .

JOURNAL OF PATHOLOGY, 2013, 230 (03) :291-297

[2] The Multifaceted Roles of STAT3 Signaling in the Progression of Prostate Cancer [J].

Bishop, Jennifer L. ;

Thaper, Daksh ;

Zoubeidi, Amina .

CANCERS, 2014, 6 (02) :829-859

[3] The STAT3 Inhibitor Galiellalactone Effectively Reduces Tumor Growth and Metastatic Spread in an Orthotopic Xenograft Mouse Model of Prostate Cancer [J].

Canesin, Giacomo ;

Evans-Axelsson, Susan ;

Hellsten, Rebecka ;

Sterner, Olov ;

Krzyzanowska, Agnieszka ;

Andersson, Tommy ;

Bjartell, Anders .

EUROPEAN UROLOGY, 2016, 69 (03) :400-404

[4] Meta-Analysis Evaluating the Impact of Site of Metastasis on Overall Survival in Men With Castration-Resistant Prostate Cancer [J].

Halabi, Susan ;

Kelly, William Kevin ;

Ma, Hua ;

Zhou, Haojin ;

Solomon, Nicole C. ;

Fizazi, Karim ;

Tangen, Catherine M. ;

Rosenthal, Mark ;

Petrylak, Daniel P. ;

Hussain, Maha ;

Vogelzang, Nicholas J. ;

Thompson, Ian M. ;

Chi, Kim N. ;

de Bono, Johann ;

Armstrong, Andrew J. ;

Eisenberger, Mario A. ;

Fandi, Abderrahim ;

Li, Shaoyi ;

Araujo, John C. ;

Logothetis, Christopher J. ;

Quinn, David I. ;

Morris, Michael J. ;

Higano, Celestia S. ;

Tannock, Ian F. ;

Small, Eric J. .

JOURNAL OF CLINICAL ONCOLOGY, 2016, 34 (14) :1652-U191

[5] Osteoblasts induce prostate cancer proliferation and PSA expression through interleukin-6-mediated activation of the androgen receptor [J].

Lu, Y ;

Zhang, J ;

Dai, JL ;

Dehne, LA ;

Mizokami, A ;

Yao, Z ;

Keller, ET .

CLINICAL & EXPERIMENTAL METASTASIS, 2004, 21 (05) :399-408

[6]

Mora LB, 2002, CANCER RES, V62, P6659

[7] Phenotypic heterogeneity of end-stage prostate carcinoma metastatic to bone [J].

Roudier, MP ;

True, LD ;

Higano, CS ;

Vesselle, H ;

Ellis, W ;

Lange, P ;

Vessella, RL .

HUMAN PATHOLOGY, 2003, 34 (07) :646-653

[8] Plasma levels of interleukin-6 and its soluble receptor are associated with prostate cancer progression and metastasis [J].

Shariat, SF ;

Andrews, B ;

Kattan, MW ;

Kim, J ;

Wheeler, TM ;

Slawin, KM .

UROLOGY, 2001, 58 (06) :1008-1015

[9] Expression levels of the JAK/STAT pathway in the transition from hormone-sensitive to hormone-refractory prostate cancer [J].

Tam, L. ;

McGlynn, L. M. ;

Traynor, P. ;

Mukherjee, R. ;

Bartlett, J. M. S. ;

Edwards, J. .

BRITISH JOURNAL OF CANCER, 2007, 97 (03) :378-383

[10] A Paracrine Role for IL6 in Prostate Cancer Patients: Lack of Production by Primary or Metastatic Tumor Cells [J].

Yu, Shu-Han ;

Zheng, Qizhi ;

Esopi, David ;

Macgregor-Das, Anne ;

Luo, Jun ;

Antonarakis, Emmanuel S. ;

Drake, Charles G. ;

Vessella, Robert ;

Morrissey, Colm ;

De Marzo, Angelo M. ;

Sfanos, Karen S. .

CANCER IMMUNOLOGY RESEARCH, 2015, 3 (10) :1175-1184

← 1 →