Abstract

Clear cell renal cell carcinoma (ccRCC) is a gender-biased tumor. Here we report that there is also a gender difference between pulmonary metastasis and lymph node metastasis showing that the androgen receptor (AR)-positive ccRCC may prefer to metastasize to lung rather than to lymph nodes. A higher AR expression increases ccRCC hematogenous metastasis yet decreases ccRCC lymphatic metastases. Mechanism dissection indicates that AR enhances miR-185-5p expression via binding to the androgen response elements located on the promoter of miR-185-5p, which suppresses VEGF-C expression via binding to its 3′ UTR. In contrast, AR-enhanced miR-185-5p also promotes HIF2α/VEGF-A expression via binding to the promoter region of HIF2α. Together, these results provide a unique mechanism by which AR can either increase or decrease ccRCC metastasis at different sites and may help us to develop combined therapies using anti-AR and anti-VEGF-C compounds to better suppress ccRCC progression.

Details

Title
Androgen receptor increases hematogenous metastasis yet decreases lymphatic metastasis of renal cell carcinoma
Author
Huang, Qingbo 1 ; Sun, Yin 2 ; Ma, Xin 3 ; Gao, Yu 3 ; Li, Xintao 3 ; Niu, Yuanjie 4 ; Zhang, Xu 3 ; Chang, Chawnshang 5 

 Department of Urology, Chinese PLA General Hospital, Beijing, China; George Whipple Lab for Cancer Research, Departments of Pathology, Urology, Radiation Oncology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA 
 George Whipple Lab for Cancer Research, Departments of Pathology, Urology, Radiation Oncology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA 
 Department of Urology, Chinese PLA General Hospital, Beijing, China 
 Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology, Tianjin Medical University, Tianjin, China 
 George Whipple Lab for Cancer Research, Departments of Pathology, Urology, Radiation Oncology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA; Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology, Tianjin Medical University, Tianjin, China; Sex Hormone Research Center, China Medical University/Hospital, Taichung, Taiwan 
Pages
1-15
Publication year
2017
Publication date
Oct 2017
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1950623038
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.