Journal
JOURNAL OF BIOMEDICAL RESEARCH
Volume 32, Issue 5, Pages 343-353Publisher
NANJING MEDICAL UNIV
DOI: 10.7555/JBR.32.20180035
Keywords
prostate cancer; metastasis; NF-kappa B; Bay 11-7082; EMT
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Funding
- National Natural Science Foundation of China (NSFC) [81272415, 81171993]
- NSFC Key Project [81130046]
- Guangxi Key Projects [2013-GXNSFEA053004]
- Guangxi Projects [2014GXNS-FDA118030]
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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-kappa B pathway was activated, which could be reversed by Bay 11-7082, a NF-kappa B pathway inhibitor. These results indicate that the cells in different culture conditions manifested significantly different biological behaviors and the NF-kappa B pathway is a potential therapeutic target for prostate cancer bone metastasis.
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