Prostate cancer tends to metastasize in the bone-mimicking microenvironment via activating NF-kB signaling

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.

Keywords

prostate cancer / metastasis / NF-kB / Bay 11-7082 / EMT

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Acknowledgments

The authors thank Xia Liu and Xin Huang for discussion and editing. We would like to thank native speaker Katrien for English language editing. This work was supported by National Natural Science Foundation of China (NSFC) (81272415 and 81171993) and NSFC Key Project (81130046); Guangxi Key Projects (2013-GXNSFEA053004); Guangxi Projects (2014GXNS-FDA118030).

RIGHTS & PERMISSIONS

2018 2018 by the Journal of Biomedical Research.