PMID- 28831065 OWN - NLM STAT- MEDLINE DCOM- 20190321 LR - 20190321 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 7 IP - 1 DP - 2017 Aug 22 TI - Reactive oxygen species-mediated switching expression of MMP-3 in stromal fibroblasts and cancer cells during prostate cancer progression. PG - 9065 LID - 10.1038/s41598-017-08835-9 [doi] LID - 9065 AB - 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-kappaB (NF-kappaB), indicating that NF-kappaB 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. FAU - Hsieh, Chia-Ling AU - Hsieh CL AD - The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. FAU - Liu, Che-Ming AU - Liu CM AD - The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. AD - The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung, Taiwan. FAU - Chen, Hsin-An AU - Chen HA AD - Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. AD - Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan. AD - Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Yang, Shun-Tai AU - Yang ST AD - Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. AD - Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. AD - Department of Neurosurgery, Shuang Ho Hospital, Taipei Medical University Taiwan, Taipei, Taiwan. FAU - Shigemura, Katsumi AU - Shigemura K AD - Department of Urology, Kobe University Hospital, Kobe, Japan. AD - Department of International Health, Kobe University Graduate School of Health Science, Kobe, Japan. FAU - Kitagawa, Koichi AU - Kitagawa K AD - Department of Urology, Kobe University Hospital, Kobe, Japan. AD - Department of International Health, Kobe University Graduate School of Health Science, Kobe, Japan. FAU - Yamamichi, Fukashi AU - Yamamichi F AD - Department of Urology, Hyogo Prefectural Amagasaki Hospital, Amagasaki, Hyogo Prefecture, 660-0828, Japan. FAU - Fujisawa, Masato AU - Fujisawa M AD - Department of Urology, Kobe University Hospital, Kobe, Japan. AD - Department of International Health, Kobe University Graduate School of Health Science, Kobe, Japan. FAU - Liu, Yun-Ru AU - Liu YR AD - Joint Biobank, Office of Human Research, Taipei Medical University, Taipei, Taiwan. FAU - Lee, Wei-Hua AU - Lee WH AD - Department of Pathology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan. FAU - Chen, Kuan-Chou AU - Chen KC AD - Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. AD - Department of Urology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan. AD - Department of Urology, College of Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Shen, Chia-Ning AU - Shen CN AUID- ORCID: 0000-0002-0747-217X AD - The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung, Taiwan. AD - Genomic Research Center, Academia Sinica, Taipei, Taiwan. FAU - Lin, Cheng-Chieh AU - Lin CC AD - The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung, Taiwan. FAU - Chung, Leland W K AU - Chung LWK AD - Uro-oncology Research Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA. FAU - Sung, Shian-Ying AU - Sung SY AD - The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. ssung@tmu.edu.tw. AD - Joint Clinical Research Center, Office of Human Research, Taipei Medical University, Taipei, Taiwan. ssung@tmu.edu.tw. LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20170822 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (MIRN128 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Reactive Oxygen Species) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Cancer-Associated Fibroblasts/metabolism/pathology MH - Carcinoma/genetics/metabolism/pathology MH - Fibroblasts/*metabolism MH - *Gene Expression Regulation MH - Humans MH - Hydrogen Peroxide/metabolism MH - Male MH - Matrix Metalloproteinase 3/*genetics/metabolism MH - MicroRNAs/genetics MH - Prostatic Neoplasms/*genetics/*metabolism/pathology MH - Reactive Oxygen Species/*metabolism MH - Stromal Cells/*metabolism PMC - PMC5567216 COIS- The authors declare that they have no competing interests. EDAT- 2017/08/24 06:00 MHDA- 2019/03/22 06:00 PMCR- 2017/08/22 CRDT- 2017/08/24 06:00 PHST- 2017/04/03 00:00 [received] PHST- 2017/07/17 00:00 [accepted] PHST- 2017/08/24 06:00 [entrez] PHST- 2017/08/24 06:00 [pubmed] PHST- 2019/03/22 06:00 [medline] PHST- 2017/08/22 00:00 [pmc-release] AID - 10.1038/s41598-017-08835-9 [pii] AID - 8835 [pii] AID - 10.1038/s41598-017-08835-9 [doi] PST - epublish SO - Sci Rep. 2017 Aug 22;7(1):9065. doi: 10.1038/s41598-017-08835-9.