title: LIM domain only 2 over-expression in prostate stromal cells facilitates prostate cancer progression through paracrine of Interleukin-11.
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.
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Chen-Yi
authors.initials: CY
authors.lastname: Jiang
authors.affiliation: Department of Urology, Subei People's Hospital of Jiangsu Province, Clinical Medical College of Yangzhou University, Yangzhou 225001, China.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Yu
authors.affiliation: Department of Urology, Shanghai General Hospital Affiliated to Nanjing Medical University, Shanghai 200080, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ruan
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Xiao-Hai
authors.initials: XH
authors.lastname: Wang
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Xing-Jie
authors.initials: XJ
authors.lastname: Wang
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Zhu
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Kui-Yuan
authors.initials: KY
authors.lastname: Hao
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Bang-Min
authors.initials: BM
authors.lastname: Han
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.|Department of Urology, Shanghai General Hospital Affiliated to Nanjing Medical University, Shanghai 200080, China.
authors.forename: Shu-Jie
authors.initials: SJ
authors.lastname: Xia
authors.affiliation: Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Fu-Jun
authors.initials: FJ
authors.lastname: Zhao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D000818:Animals; D018450:Disease Progression; D064593:Heterografts; D006801:Humans; D017370:Interleukin-11 / Q000096:biosynthesis*; D060588:LIM Domain Proteins / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D019899:Paracrine Communication / Q000502:physiology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C508611:IL11 protein, human; D017370:Interleukin-11; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; D011518:Proto-Oncogene Proteins
keywords: Interleukin-11 (IL-11); LIM domain only 2 (LMO2); prostate cancer; stromal cell; stromal-epithelial crosstalk