Abstract
Abstract Crosstalk between cancer and milieu cells plays a central role during cancer progression, which includes determine the faith of increasing metalloproteinase secretion by cancer epithelial cells. Here, we showed prostate tumor and stromal fibroblasts expressed opposite levels of Stromelysin-1 and -2 in both 3D co-culture and paired patient samples. Macroarray and quantitative RT-PCR studies demonstrated significantly decreased of Stromelysin-1 expression in co-cultured HS27AC4-2 and 4 paired tumor associated fibroblasts that were collected in previous report. We noticed the Stromelysin-1 expression level was decreased in stromal region of prostate cancer. By contrast, Stromelysin-1 level was increased in malignant cancer epithelial cells in both cells and tissue staining. Canonical pathway study revealed of differentially gene expression between HS27AC4-2 and HS27ARWV including the majority of pathway enrichment in TGF-β and hydrogen peroxide as central mediators. Induction of Stromelysin-1 and -2 by TGF-β and/or hydrogen peroxide were preliminary validated in the conditioned medium of prostate cancer cells, PC3 and DU145, and paired patient stromal fibroblasts that confirmed the opposite regulation of Stromelysin-1 and -2 expression by hydrogen peroxide but not TGF-β. Our results demonstrate the differential regulation of Stromelysin-1 and -2 expression in prostate cancer cells and stromal fibroblasts through ROS, such as hydrogen peroxide, as mediator and shed the light on the potentially useful as indication for the differential regulation between cancer and stromal cells. Citation Format: Shian-Ying Sung, Chia-Ling Hsieh. Opposite regulation of stromelysin expression in prostate tumor and its microenvironment. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 361. doi:10.1158/1538-7445.AM2015-361
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