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

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Abstract

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.

Original languageEnglish
Article number9065
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

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Matrix Metalloproteinase 3
Reactive Oxygen Species
Prostatic Neoplasms
Fibroblasts
Neoplasms
Hydrogen Peroxide
Extracellular Matrix
Tumor Microenvironment
Coculture Techniques
MicroRNAs
Cancer-Associated Fibroblasts
Homeostasis
Growth

ASJC Scopus subject areas

  • General

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Reactive oxygen species-mediated switching expression of MMP-3 in stromal fibroblasts and cancer cells during prostate cancer progression. / Hsieh, Chia Ling; Liu, Che Ming; Chen, Hsin An; Yang, Shun Tai; Shigemura, Katsumi; Kitagawa, Koichi; Yamamichi, Fukashi; Fujisawa, Masato; Liu, Yun Ru; Lee, Wei Hua; Chen, Kuan Chou; Shen, Chia Ning; Lin, Cheng Chieh; Chung, Leland W.K.; Sung, Shian Ying.

In: Scientific Reports, Vol. 7, No. 1, 9065, 01.12.2017.

Research output: Contribution to journalArticle

Hsieh, Chia Ling ; Liu, Che Ming ; Chen, Hsin An ; Yang, Shun Tai ; Shigemura, Katsumi ; Kitagawa, Koichi ; Yamamichi, Fukashi ; Fujisawa, Masato ; Liu, Yun Ru ; Lee, Wei Hua ; Chen, Kuan Chou ; Shen, Chia Ning ; Lin, Cheng Chieh ; Chung, Leland W.K. ; Sung, Shian Ying. / Reactive oxygen species-mediated switching expression of MMP-3 in stromal fibroblasts and cancer cells during prostate cancer progression. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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