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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doaj-b3c9b9a6d5f74bdda45fa2a9e1e37c222020-12-08T02:22:14ZengNature Publishing GroupScientific Reports2045-23222017-08-017111410.1038/s41598-017-08835-9Reactive oxygen species–mediated switching expression of MMP-3 in stromal fibroblasts and cancer cells during prostate cancer progressionChia-Ling Hsieh0Che-Ming Liu1Hsin-An Chen2Shun-Tai Yang3Katsumi Shigemura4Koichi Kitagawa5Fukashi Yamamichi6Masato Fujisawa7Yun-Ru Liu8Wei-Hua Lee9Kuan-Chou Chen10Chia-Ning Shen11Cheng-Chieh Lin12Leland W. K. Chung13Shian-Ying Sung14The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical UniversityThe Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical UniversityDepartment of Surgery, School of Medicine, College of Medicine, Taipei Medical UniversityDepartment of Surgery, School of Medicine, College of Medicine, Taipei Medical UniversityDepartment of Urology, Kobe University HospitalDepartment of Urology, Kobe University HospitalDepartment of Urology, Hyogo Prefectural Amagasaki HospitalDepartment of Urology, Kobe University HospitalJoint Biobank, Office of Human Research, Taipei Medical UniversityDepartment of Pathology, Shuang Ho Hospital, Taipei Medical UniversityGraduate Institute of Clinical Medicine, College of Medicine, Taipei Medical UniversityThe Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia SinicaThe Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia SinicaUro-oncology Research Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical CenterThe Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical UniversityAbstract 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.https://doi.org/10.1038/s41598-017-08835-9 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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 |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-08-01 |
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. |
url |
https://doi.org/10.1038/s41598-017-08835-9 |
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