Androgen receptor in human prostate cancer-associated fibroblasts promotes prostate cancer epithelial cell growth and invasion

被引:61
作者
Yu, Shengqiang [1 ,2 ,3 ,4 ,5 ]
Xia, Shujie [5 ]
Yang, Diandong [1 ]
Wang, Ke [1 ]
Yeh, Shuyuan [2 ,3 ,4 ]
Gao, Zhenli [1 ]
Chang, Chawnshang [2 ,3 ,4 ]
机构
[1] Qingdao Univ, Coll Med, Yantai Yuhuangding Hosp, Dept Urol, Yantai 264000, Shandong, Peoples R China
[2] Univ Rochester, Med Ctr, George Whipple Lab Canc Res, Dept Pathol, Rochester, NY 14642 USA
[3] Univ Rochester, Med Ctr, Dept Urol, Rochester, NY 14642 USA
[4] Univ Rochester, Med Ctr, Wilmot Canc Ctr, Rochester, NY 14642 USA
[5] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 1, Dept Urol, Shanghai 200080, Peoples R China
关键词
Prostate cancer; Androgen receptor; Cancer-associated fibroblasts; Primary culture; Growth factors; DEPRIVATION THERAPY; REACTIVE STROMA; EXPRESSION;
D O I
10.1007/s12032-013-0674-9
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The androgens and androgen receptor (AR) play key roles in the prostate cancer (PCa) development and progression via epithelium-stroma cross talk. Prostate cancer-associated fibroblasts (CAFs) are dominant components in PCa stroma and are essential in the malignant progression by supporting tumorigenesis and metastasis. However, the AR roles in CAFs are still obscure. We isolated and immortalized the CAFs from human PCa tissues and found the CAFs are AR positive. We then knocked down their AR with siRNA and co-cultured the resultant CAFs with PCa cell line PC3. The MTT, invasion, and colony formation assays were performed to study the PC3 biological behavior. The results showed that the PCa epithelial growth, invasion, and colony formation abilities decreased when knocking down the CAFs AR. By using the real-time quantitative polymerase chain reaction, we found the IGF1, FGF7, FGF10, SDF1, HGF, and TGFb2 expression levels decreased in the AR knocked down CAFs. These results suggested that the AR in CAFs promoted PCa epithelial growth and invasion via regulating a series of growth factors. Targeting the AR in CAFs might be a potential therapeutic option for PCa in future.
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页数:7
相关论文
共 21 条
[1]   Dissociation of epithelial and neuroendocrine carcinoma lineages in the transgenic adenocarcinoma of mouse prostate model of prostate cancer [J].
Chiaverotti, Teresa ;
Couto, Suzana S. ;
Donjacour, Annemarie ;
Mao, Jian-Hua ;
Nagase, Hiroki ;
Cardiff, Robert D. ;
Cunha, Gerald R. ;
Balmain, Allan .
AMERICAN JOURNAL OF PATHOLOGY, 2008, 172 (01) :236-246
[2]   ANDROGEN RECEPTOR EXPRESSION IN DEVELOPING MALE REPRODUCTIVE-ORGANS [J].
COOKE, PS ;
YOUNG, P ;
CUNHA, GR .
ENDOCRINOLOGY, 1991, 128 (06) :2867-2873
[3]   Mesenchymal-epithelial interactions: past, present, and future [J].
Cunha, Gerald R. .
DIFFERENTIATION, 2008, 76 (06) :578-586
[4]   Global Gene Expression Analysis of Reactive Stroma in Prostate Cancer [J].
Dakhova, Olga ;
Ozen, Mustafa ;
Creighton, Chad J. ;
Li, Rile ;
Ayala, Gustavo ;
Rowley, David ;
Ittmann, Michael .
CLINICAL CANCER RESEARCH, 2009, 15 (12) :3979-3989
[5]   Cancer Associated Fibroblasts Exploit Reactive Oxygen Species Through a Proinflammatory Signature Leading to Epithelial Mesenchymal Transition and Stemness [J].
Giannoni, Elisa ;
Bianchini, Francesca ;
Calorini, Lido ;
Chiarugi, Paola .
ANTIOXIDANTS & REDOX SIGNALING, 2011, 14 (12) :2361-2371
[6]   Reciprocal Activation of Prostate Cancer Cells and Cancer-Associated Fibroblasts Stimulates Epithelial-Mesenchymal Transition and Cancer Stemness [J].
Giannoni, Elisa ;
Bianchini, Francesca ;
Masieri, Lorenzo ;
Serni, Sergio ;
Torre, Eugenio ;
Calorini, Lido ;
Chiarugi, Paola .
CANCER RESEARCH, 2010, 70 (17) :6945-6956
[7]   Safety and tolerability of intermittent androgen deprivation therapy: A literature review [J].
Gruca, Damian ;
Bacher, Peter ;
Tunn, Ulf .
INTERNATIONAL JOURNAL OF UROLOGY, 2012, 19 (07) :614-625
[8]   Development of two androgen receptor assays using adenoviral transduction of MMTV-Luc reporter and/or hAR for endocrine screening [J].
Hartig, PC ;
Bobseine, KL ;
Britt, BH ;
Cardon, MC ;
Lambright, CR ;
Wilson, VS ;
Gray, LE .
TOXICOLOGICAL SCIENCES, 2002, 66 (01) :82-90
[9]  
Hayward SW, 2001, CANCER RES, V61, P8135
[10]   Androgen receptor in prostate cancer [J].
Heinlein, CA ;
Chang, CS .
ENDOCRINE REVIEWS, 2004, 25 (02) :276-308