Interleukin‐17 promotes development of castration‐resistant prostate cancer potentially through creating an immunotolerant and pro‐angiogenic tumor microenvironment. Issue 8 (1st April 2014)

• Record Type: Journal Article
• Authors: Zhang, Qiuyang; Liu, Sen; Zhang, Qingsong; Xiong, Zhenggang; Wang, Alun R.; Myers, Leann; Melamed, Jonathan; Tang, Wendell W.; You, Zongbing
• Is Part Of: Prostate. Volume 74:Issue 8(2014)
• Page Start: 869
• Page End: 879
• Publication Date: 2014-04-01
• Subjects: Prostate -- Diseases -- Periodicals; 616
• DOI: 10.1002/pros.22805
• Languages: English
• ISSNs: 0270-4137

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="pros22805-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>Interleukin‐17 (IL‐17) has been demonstrated to promote formation and growth of hormone‐naïve prostate adenocarcinoma in mice. IL‐17's role in development of castration‐resistant prostate cancer is unknown. In the present study, we investigated IL‐17's role in castration‐resistant prostate cancer in a mouse model.</p> </sec> <sec id="pros22805-sec-0002" sec-type="section"> <title>METHODS</title> <p>IL‐17 receptor C (IL‐17RC) deficient mice were interbred with <italic>Pten</italic> conditional mutant mice to produce RC<sup>+</sup> mice that maintained IL‐17RC expression and RC<sup>−</sup> mice that were IL‐17RC deficient. Male RC<sup>+</sup> and RC<sup>−</sup> mice were <italic>Pten</italic>‐null and were castrated at 16 weeks of age when invasive prostate cancer had already formed. At 30 weeks of age, all male mice were analyzed for the prostate phenotypes.</p> </sec> <sec id="pros22805-sec-0003" sec-type="section"> <title>RESULTS</title> <p>RC<sup>−</sup> mice displayed prostates that were smaller than RC<sup>+</sup> mice. Approximately 23% of prostatic glands in RC<sup>−</sup> mice, in contrast to 65% of prostatic glands in RC<sup>+</sup> mice, developed invasive adenocarcinomas. Compared to castrate RC<sup>+</sup> mice, castrate RC<sup>−</sup> mouse prostate had lower rates of cellular proliferation and higher rates of apoptosis as well as lower levels of MMP7, YBX1, MTA1, and UBE2C proteins. In addition, castrate RC<sup>−</sup> mouse prostate had less angiogenesis, which was associated with decreased levels of COX‐2 and VEGF. Moreover, castrate RC<sup>−</sup> mouse prostate had fewer inflammatory cells including lymphocytes, myeloid‐derived suppressor cells, and macrophages.</p> </sec> <sec id="pros22805-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>Taken together, our findings suggest that IL‐17 promotes development of invasive prostate adenocarcinomas under castrate conditions, potentially through creating an immunotolerant and pro‐angiogenic tumor microenvironment. <italic>Prostate 74:869–879, 2014</italic>. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>