Skip to main content
Top
Published in: Medical Oncology 3/2013

01-09-2013 | Original Paper

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

Authors: Shengqiang Yu, Shujie Xia, Diandong Yang, Ke Wang, Shuyuan Yeh, Zhenli Gao, Chawnshang Chang

Published in: Medical Oncology | Issue 3/2013

Login to get access

Abstract

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.
Literature
1.
2.
go back to reference Ian LH, Li H, Yang Y, Ho CF. Comparisons of the incidence and pathological characteristics of prostate cancer between Chinese and Portuguese in Macau. Chin Med J (Engl). 2008;121:292–4. Ian LH, Li H, Yang Y, Ho CF. Comparisons of the incidence and pathological characteristics of prostate cancer between Chinese and Portuguese in Macau. Chin Med J (Engl). 2008;121:292–4.
3.
4.
go back to reference Miyamoto H, Messing EM, Chang C. Androgen deprivation therapy for prostate cancer: current status and future prospects. Prostate. 2004;61:332–53.PubMedCrossRef Miyamoto H, Messing EM, Chang C. Androgen deprivation therapy for prostate cancer: current status and future prospects. Prostate. 2004;61:332–53.PubMedCrossRef
5.
go back to reference Gruca D, Bacher P, Tunn U. Safety and tolerability of intermittent androgen deprivation therapy: a literature review. Int J Urol. 2012;19:614–25.PubMedCrossRef Gruca D, Bacher P, Tunn U. Safety and tolerability of intermittent androgen deprivation therapy: a literature review. Int J Urol. 2012;19:614–25.PubMedCrossRef
6.
go back to reference Lin Y, Lu Z, Kokontis J, Xiang J. Androgen receptor primes prostate cancer cells to apoptosis through down-regulation of basal p21 expression. Biochem Biophys Res Commun. 2013;430:289–93.PubMedCrossRef Lin Y, Lu Z, Kokontis J, Xiang J. Androgen receptor primes prostate cancer cells to apoptosis through down-regulation of basal p21 expression. Biochem Biophys Res Commun. 2013;430:289–93.PubMedCrossRef
7.
go back to reference Yu SQ, Lai KP, Xia SJ, Chang HC, Chang C, Yeh S. The diverse and contrasting effects of using human prostate cancer cell lines to study androgen receptor roles in prostate cancer. Asian J Androl. 2009;11:39–48.PubMedCrossRef Yu SQ, Lai KP, Xia SJ, Chang HC, Chang C, Yeh S. The diverse and contrasting effects of using human prostate cancer cell lines to study androgen receptor roles in prostate cancer. Asian J Androl. 2009;11:39–48.PubMedCrossRef
8.
go back to reference Giannoni E, Bianchini F, Calorini L, Chiarugi P. Cancer associated fibroblasts exploit reactive oxygen species through a proinflammatory signature leading to epithelial mesenchymal transition and stemness. Antioxid Redox Signal. 2011;14:2361–71.PubMedCrossRef Giannoni E, Bianchini F, Calorini L, Chiarugi P. Cancer associated fibroblasts exploit reactive oxygen species through a proinflammatory signature leading to epithelial mesenchymal transition and stemness. Antioxid Redox Signal. 2011;14:2361–71.PubMedCrossRef
9.
go back to reference Ilio KY, Nemeth JA, Lang S, Lee C. The primary culture of rat prostate basal cells. J Androl. 1998;19:718–24.PubMed Ilio KY, Nemeth JA, Lang S, Lee C. The primary culture of rat prostate basal cells. J Androl. 1998;19:718–24.PubMed
10.
go back to reference Yu S, Zhang C, Lin CC, Niu Y, Lai KP, Chang HC, et al. Altered prostate epithelial development and IGF-1 signal in mice lacking the androgen receptor in stromal smooth muscle cells. Prostate. 2011;71:517–24.PubMedCrossRef Yu S, Zhang C, Lin CC, Niu Y, Lai KP, Chang HC, et al. Altered prostate epithelial development and IGF-1 signal in mice lacking the androgen receptor in stromal smooth muscle cells. Prostate. 2011;71:517–24.PubMedCrossRef
11.
go back to reference Olumi AF, Grossfeld GD, Hayward SW, Carroll PR, Tlsty TD, Cunha GR. Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res. 1999;59:5002–11.PubMed Olumi AF, Grossfeld GD, Hayward SW, Carroll PR, Tlsty TD, Cunha GR. Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res. 1999;59:5002–11.PubMed
12.
go back to reference Hartig PC, Bobseine KL, Britt BH, Cardon MC, Lambright CR, Wilson VS, et al. Development of two androgen receptor assays using adenoviral transduction of MMTV-luc reporter and/or hAR for endocrine screening. Toxicol Sci. 2002;66:82–90.PubMedCrossRef Hartig PC, Bobseine KL, Britt BH, Cardon MC, Lambright CR, Wilson VS, et al. Development of two androgen receptor assays using adenoviral transduction of MMTV-luc reporter and/or hAR for endocrine screening. Toxicol Sci. 2002;66:82–90.PubMedCrossRef
13.
go back to reference Cooke PS, Young P, Cunha GR. Androgen receptor expression in developing male reproductive organs. Endocrinology. 1991;128:2867–73.PubMedCrossRef Cooke PS, Young P, Cunha GR. Androgen receptor expression in developing male reproductive organs. Endocrinology. 1991;128:2867–73.PubMedCrossRef
14.
go back to reference Cunha GR. Mesenchymal-epithelial interactions: past, present, and future. Differentiation. 2008;76:578–86.PubMedCrossRef Cunha GR. Mesenchymal-epithelial interactions: past, present, and future. Differentiation. 2008;76:578–86.PubMedCrossRef
15.
go back to reference Niu Y, Altuwaijri S, Yeh S, Lai KP, Yu S, Chuang KH, et al. Targeting the stromal androgen receptor in primary prostate tumors at earlier stages. Proc Natl Acad Sci USA. 2008;105:12188–93.PubMedCrossRef Niu Y, Altuwaijri S, Yeh S, Lai KP, Yu S, Chuang KH, et al. Targeting the stromal androgen receptor in primary prostate tumors at earlier stages. Proc Natl Acad Sci USA. 2008;105:12188–93.PubMedCrossRef
16.
go back to reference Chiaverotti T, Couto SS, Donjacour A, Mao JH, Nagase H, Cardiff RD, et al. Dissociation of epithelial and neuroendocrine carcinoma lineages in the transgenic adenocarcinoma of mouse prostate model of prostate cancer. Am J Pathol. 2008;172:236–46.PubMedCrossRef Chiaverotti T, Couto SS, Donjacour A, Mao JH, Nagase H, Cardiff RD, et al. Dissociation of epithelial and neuroendocrine carcinoma lineages in the transgenic adenocarcinoma of mouse prostate model of prostate cancer. Am J Pathol. 2008;172:236–46.PubMedCrossRef
17.
go back to reference Dakhova O, Ozen M, Creighton CJ, Li R, Ayala G, Rowley D, et al. Global gene expression analysis of reactive stroma in prostate cancer. Clin Cancer Res. 2009;15:3979–89.PubMedCrossRef Dakhova O, Ozen M, Creighton CJ, Li R, Ayala G, Rowley D, et al. Global gene expression analysis of reactive stroma in prostate cancer. Clin Cancer Res. 2009;15:3979–89.PubMedCrossRef
18.
go back to reference Tuxhorn JA, Ayala GE, Rowley DR. Reactive stroma in prostate cancer progression. J Urol. 2001;166:2472–83.PubMedCrossRef Tuxhorn JA, Ayala GE, Rowley DR. Reactive stroma in prostate cancer progression. J Urol. 2001;166:2472–83.PubMedCrossRef
19.
go back to reference Hayward SW, Wang Y, Cao M, Hom YK, Zhang B, Grossfeld GD, et al. Malignant transformation in a nontumorigenic human prostatic epithelial cell line. Cancer Res. 2001;61:8135–42.PubMed Hayward SW, Wang Y, Cao M, Hom YK, Zhang B, Grossfeld GD, et al. Malignant transformation in a nontumorigenic human prostatic epithelial cell line. Cancer Res. 2001;61:8135–42.PubMed
20.
go back to reference Giannoni E, Bianchini F, Masieri L, Serni S, Torre E, Calorini L, et al. Reciprocal activation of prostate cancer cells and cancer-associated fibroblasts stimulates epithelial-mesenchymal transition and cancer stemness. Cancer Res. 2010;70:6945–56.PubMedCrossRef Giannoni E, Bianchini F, Masieri L, Serni S, Torre E, Calorini L, et al. Reciprocal activation of prostate cancer cells and cancer-associated fibroblasts stimulates epithelial-mesenchymal transition and cancer stemness. Cancer Res. 2010;70:6945–56.PubMedCrossRef
21.
go back to reference Micke P, Ostman A. Tumour-stroma interaction: cancer-associated fibroblasts as novel targets in anti-cancer therapy? Lung Cancer. 2004;45(Suppl 2):S163–75.PubMedCrossRef Micke P, Ostman A. Tumour-stroma interaction: cancer-associated fibroblasts as novel targets in anti-cancer therapy? Lung Cancer. 2004;45(Suppl 2):S163–75.PubMedCrossRef
Metadata
Title
Androgen receptor in human prostate cancer-associated fibroblasts promotes prostate cancer epithelial cell growth and invasion
Authors
Shengqiang Yu
Shujie Xia
Diandong Yang
Ke Wang
Shuyuan Yeh
Zhenli Gao
Chawnshang Chang
Publication date
01-09-2013
Publisher
Springer US
Published in
Medical Oncology / Issue 3/2013
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-013-0674-9

Other articles of this Issue 3/2013

Medical Oncology 3/2013 Go to the issue