Reactive oxygen species-mediated switching expression of MMP-3 in stromal fibroblasts and cancer cells during prostate cancer progression

Chia Ling Hsieh, Che Ming Liu, Hsin An Chen, Shun Tai Yang, Katsumi Shigemura, Koichi Kitagawa, Fukashi Yamamichi, Masato Fujisawa, Yun Ru Liu, Wei Hua Lee, Kuan Chou Chen, Chia Ning Shen, Cheng Chieh Lin, Leland W.K. Chung, Shian Ying Sung

研究成果: 雜誌貢獻文章

8 引文 斯高帕斯(Scopus)

摘要

Studies on the aberrant control of extracellular matrices (ECMs) have mainly focused on the role of malignant cells but less on that of stromal fibroblasts during cancer development. Herein, by using paired normal and prostate cancer-associated stromal fibroblasts (CAFs) derived from a coculture cell model and clinical patient samples, we demonstrated that although CAFs promoted prostate cancer growth, matrix metalloproteinase-3 (MMP-3) was lower in CAFs but elevated in prostate cancer cells relative to their normal counterparts. Furthermore, hydrogen peroxide was characterized as the central modulator for altered MMP-3 expression in prostate cancer cells and CAFs, but through different regulatory mechanisms. Treatment of CAFs but not prostate cancer cells with hydrogen peroxide directly inhibited mmp-3 promoter activity with concomitant nuclear translocation of nuclear factor-κB (NF-κB), indicating that NF-κB is the downstream pathway for the transcriptional repression of MMP-3 in CAFs. Hydrogen peroxide reduced thrombospondin 2 (an MMP-3 suppressor) expression in prostate cancer cells by upregulating microRNA-128. To the best of our knowledge, this is the first study to demonstrate the crucial role of reactive oxygen species in the switching expression of MMP-3 in stromal fibroblasts and prostate cancer cells during tumor progression, clarifying how the tumor microenvironment modulates ECM homeostasis control.
原文英語
文章編號9065
期刊Scientific Reports
7
發行號1
DOIs
出版狀態已發佈 - 十二月 1 2017

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