Oncotarget

Research Papers:

LIM domain only 2 over-expression in prostate stromal cells facilitates prostate cancer progression through paracrine of Interleukin-11

Chen-Yi Jiang _, Jun-Jie Yu, Yuan Ruan, Xiao-Hai Wang, Wei Zhao, Xing-Jie Wang, Yi-Ping Zhu, Yuan Gao, Kui-Yuan Hao, Lei Chen, Bang-Min Han, Shu-Jie Xia and Fu-Jun Zhao

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Oncotarget. 2016; 7:26247-26258. https://doi.org/10.18632/oncotarget.8359

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Abstract

Chen-Yi Jiang1,*, Jun-Jie Yu2,*, Yuan Ruan3, Xiao-Hai Wang1, Wei Zhao1, Xing-Jie Wang1, Yi-Ping Zhu1, Yuan Gao1, Kui-Yuan Hao1, Lei Chen1, Bang-Min Han1, Shu-Jie Xia1,3, Fu-Jun Zhao1

1Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China

2Department of Urology, Subei People’s Hospital of Jiangsu Province, Clinical Medical College of Yangzhou University, Yangzhou 225001, China

3Department of Urology, Shanghai General Hospital Affiliated to Nanjing Medical University, Shanghai 200080, China

*These authors have contributed equally to this work

Correspondence to:

Fu-Jun Zhao, e-mail: [email protected]

Shu-Jie Xia, e-mail: [email protected]

Keywords: prostate cancer, stromal cell, stromal-epithelial crosstalk, LIM domain only 2 (LMO2), Interleukin-11 (IL-11)

Received: November 16, 2015    Accepted: March 07, 2016    Published: March 25, 2016

ABSTRACT

Mechanisms of stromal-epithelial crosstalk are essential for Prostate cancer (PCa) tumorigenesis and progression. Peripheral zone of the prostate gland possesses a stronger inclination for PCa than transition zone. We previously found a variety of genes that differently expressed among different prostate stromal cells, including LIM domain only 2 (LMO2) which highly expressed in peripheral zone derived stromal cells (PZSCs) and PCa associated fibroblasts (CAFs) compared to transition zone derived stromal cells (TZSCs). Studies on its role in tumors have highlighted LMO2 as an oncogene. Herein, we aim to study the potential mechanisms of stromal LMO2 in promoting PCa progression. The in vitro cells co-culture and in vivo cells recombination revealed that LMO2 over-expressed prostate stromal cells could promote the proliferation and invasiveness of either prostate epithelial or cancer cells. Further protein array screening confirmed that stromal LMO2 stimulated the secretion of Interleukin-11 (IL-11), which could promote proliferation and invasiveness of PCa cells via IL-11 receptor α (IL11Rα) – STAT3 signaling. Moreover, stromal LMO2 over-expression could suppress miR-204-5p which was proven to be a negative regulator of IL-11 expression. Taken together, results of our study demonstrate that prostate stromal LMO2 is capable of stimulating IL-11 secretion and by which activates IL11Rα – STAT3 signaling in PCa cells and then facilitates PCa progression. These results may make stromal LMO2 responsible for zonal characteristic of PCa and as a target for PCa microenvironment-targeted therapy.


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