Reactive oxygen species–mediated switching expression of MMP-3 in stromal fibroblasts and cancer cells during prostate cancer progression
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 cocu...
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Nature Portfolio
2017
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oai:doaj.org-article:b3c9b9a6d5f74bdda45fa2a9e1e37c222021-12-02T16:07:43ZReactive oxygen species–mediated switching expression of MMP-3 in stromal fibroblasts and cancer cells during prostate cancer progression10.1038/s41598-017-08835-92045-2322https://doaj.org/article/b3c9b9a6d5f74bdda45fa2a9e1e37c222017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08835-9https://doaj.org/toc/2045-2322Abstract 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.Chia-Ling HsiehChe-Ming LiuHsin-An ChenShun-Tai YangKatsumi ShigemuraKoichi KitagawaFukashi YamamichiMasato FujisawaYun-Ru LiuWei-Hua LeeKuan-Chou ChenChia-Ning ShenCheng-Chieh LinLeland W. K. ChungShian-Ying SungNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017) |
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Medicine R Science Q 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 Reactive oxygen species–mediated switching expression of MMP-3 in stromal fibroblasts and cancer cells during prostate cancer progression |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Chia-Ling Hsieh |
| title |
Reactive oxygen species–mediated switching expression of MMP-3 in stromal fibroblasts and cancer cells during prostate cancer progression |
| title_short |
Reactive oxygen species–mediated switching expression of MMP-3 in stromal fibroblasts and cancer cells during prostate cancer progression |
| title_full |
Reactive oxygen species–mediated switching expression of MMP-3 in stromal fibroblasts and cancer cells during prostate cancer progression |
| title_fullStr |
Reactive oxygen species–mediated switching expression of MMP-3 in stromal fibroblasts and cancer cells during prostate cancer progression |
| title_full_unstemmed |
Reactive oxygen species–mediated switching expression of MMP-3 in stromal fibroblasts and cancer cells during prostate cancer progression |
| title_sort |
reactive oxygen species–mediated switching expression of mmp-3 in stromal fibroblasts and cancer cells during prostate cancer progression |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/b3c9b9a6d5f74bdda45fa2a9e1e37c22 |
| work_keys_str_mv |
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