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.

RNA‐binding protein Musashi2 stabilizing androgen receptor drives prostate cancer progression

“…The prostate cancer tissue microarray contained 61 prostate cancer tissue spots and 39 para cancer spots of 64 patients (OUTDO, Shanghai, China). immunohistochemistry (IHC) and immunofluorescence (IF) were performed as described previously . Briefly, IHC was performed on the paraffin embedded tissue microarray using anti–MSI2 (1:200).…”

Deregulation of ATG9A by impaired AR signaling induces autophagy in prostate stromal fibroblasts and promotes BPH progression

“…The balance of stromal-epithelial crosstalk in the prostate has essential physical and functional meaning for prostate development. However, in prostatic diseases, such as BPH, prostatitis, and prostate cancer, homeostasis between stromal and epithelial compartments in the tissue microenvironment is broken 22 , 24 . The stromal compartment that consists mostly of fibroblasts can occupy more than 70% of BPH tissues, suggesting that hyperproliferation of stromal fibroblasts is an essential mechanism in the pathological process of BPH 25 .…”

“…IHC and IF were performed as described previously 17 , 24 . IHC images were acquired under a Leica DM5500 B microscope.…”

5‐ARI induces autophagy of prostate epithelial cells through suppressing IGF‐1 expression in prostate fibroblasts

“…2 Reducing androgen levels has been universally recognized as an effective method for treating BPH by inducing prostate epithelial cell apoptosis. 6 Prostate epithelial cells are non-cell autonomously regulated by cytokines released by prostate fibroblasts in a paracrine manner. 4,5 The prostate consists of fibroblasts and epithelial cells, and its microenvironment is complex.…”