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Haibo Tong,Chunlin Zou,Siyuan Qin,Jie Meng,Evan T. Keller,Jian Zhang,Yi Lu.Journal of Biomedical Research,2018,32(5):343-353
Prostate cancer tends to metastasize in the bone-mimicking microenvironment via activating NF-kB signaling
Received:April 06, 2018  Revised:May 21, 2018
DOI10.7555/JBR.32.20180035
Keywordsprostate cancer, metastasis, NF-kB, Bay 11-7082, EMT
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AuthorInstitution
Haibo Tong Key Laboratory of Longevity and Aging-related Diseases, Guangxi Medical University, Ministry of Education, Nanning, Guangxi , China; Southern University of Science and Technology School of Medicine, Shenzhen, Guangdong , China;
Chunlin Zou Key Laboratory of Longevity and Aging-related Diseases, Guangxi Medical University, Ministry of Education, Nanning, Guangxi , China
Siyuan Qin Key Laboratory of Longevity and Aging-related Diseases, Guangxi Medical University, Ministry of Education, Nanning, Guangxi , China; Southern University of Science and Technology School of Medicine, Shenzhen, Guangdong , China;
Jie Meng Key Laboratory of Longevity and Aging-related Diseases, Guangxi Medical University, Ministry of Education, Nanning, Guangxi , China; Southern University of Science and Technology School of Medicine, Shenzhen, Guangdong , China;
Evan T. Keller Department of Pathology and Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
Jian Zhang Southern University of Science and Technology School of Medicine, Shenzhen, Guangdong , China;Department of Pathology and Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Yi Lu Key Laboratory of Longevity and Aging-related Diseases, Guangxi Medical University, Ministry of Education, Nanning, Guangxi , China; Southern University of Science and Technology School of Medicine, Shenzhen, Guangdong , China;
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Abstract
      Prostate cancer preferentially metastasizes to the bone. However, the underlying molecular mechanisms are still unclear. To explore the effects of a bone-mimicking microenvironment on PC3 prostate cancer cell growth and metastasis, we used osteoblast differentiation medium (ODM; minimal essential medium alpha supplemented with L-ascorbic acid) to mimic the bone microenvironment. PC3 cells grown in ODM underwent epithelial-mesenchymal transition and showed enhanced colony formation, migration, and invasion abilities compared to the cells grown in normal medium. PC3 cells grown in ODM showed enhanced metastasis when injected in mice. A screening of signaling pathways related to invasion and metastasis revealed that the NF-kB pathway was activated, which could be reversed by Bay 11-7082, a NF-kB pathway inhibitor. These results indicate that the cells in different culture conditions manifested significantly different biological behaviors and the NF-kB pathway is a potential therapeutic target for prostate cancer bone metastasis.
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